SpringerLink
Log in

Quantitative Peripheral Blood Perturbations of γδ T Cells in Human Disease and Their Clinical Implications

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

Human γδ T cells, which play innate and adaptive, protective as well as destructive, roles in the immune response, were discovered in 1986, but the clinical significance of alterations of the levels of these cells in the peripheral blood in human diseases has not been comprehensively reviewed. Here, we review patterns of easily measurable changes of this subset of T cells in peripheral blood from relevant publications in PubMed and their correlations with specific disease categories, specific diagnoses within disease categories, and prognostic outcomes. These collective data suggest that enumeration of γδ T cells and their subsets in the peripheral blood of patients could be a useful tool to evaluate diagnosis and prognosis in the clinical setting.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Davis MM et al (1984) A murine T cell receptor gene complex: isolation, structure and rearrangement. Immunol Rev 81:235–258

    CAS  PubMed  Google Scholar 

  2. Saito H et al (1984) Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. Nature 309(5971):757–762

    CAS  PubMed  Google Scholar 

  3. Royer HD et al (1984) Genes encoding the Ti beta subunit of the antigen/MHC receptor undergo rearrangement during intrathymic ontogeny prior to surface T3-Ti expression. Cell 39(2 Pt 1):261–266

    CAS  PubMed  Google Scholar 

  4. Fabbi M et al (1984) Homology of Ti alpha-subunit of a T-cell antigen-MHC receptor with immunoglobulin. Nature 312(5991):269–271

    CAS  PubMed  Google Scholar 

  5. Saito H et al (1984) A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes. Nature 312(5989):36–40

    CAS  PubMed  Google Scholar 

  6. Bank I et al (1986) A functional T3 molecule associated with a novel heterodimer on the surface of immature human thymocytes. Nature 322(6075):179–181

    CAS  PubMed  Google Scholar 

  7. Brenner MB et al (1986) Identification of a putative second T-cell receptor. Nature 322(6075):145–149

    CAS  PubMed  Google Scholar 

  8. Chien YH, Konigshofer Y (2007) Antigen recognition by gammadelta T cells. Immunol Rev 215:46–58

    CAS  PubMed  Google Scholar 

  9. Nedellec S et al (2010) Human Vgamma9Vdelta2 T cells: from signals to functions. Semin Immunol 22(4):199–206

    CAS  PubMed  Google Scholar 

  10. Kabelitz D et al (2000) Antigen recognition by human gammadelta T lymphocytes. Int Arch Allergy Immunol 122(1):1–7

    CAS  PubMed  Google Scholar 

  11. Palakodeti A et al (2013) The molecular basis for modulation of human Vgamma9Vdelta2 T cell responses by CD277/butyrophilin-3 (BTN3A)-specific antibodies. J Biol Chem 287(39):32780–32790

    Google Scholar 

  12. Bai L et al (2012) The majority of CD1d-sulfatide-specific T cells in human blood use a semiinvariant Vdelta1 TCR. Eur J Immunol 42(9):2505–2510

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Bonneville M et al (2010) Gammadelta T cell effector functions: a blend of innate programming and acquired plasticity. Nat Rev Immunol 10(7):467–478

    CAS  PubMed  Google Scholar 

  14. Born WK et al (2011) Peptide antigens for gamma/delta T cells. Cell Mol Life Sci 68(14):2335–2343

    CAS  PubMed  Google Scholar 

  15. Hayday AC (2000) [gamma][delta] cells: a right time and a right place for a conserved third way of protection. Annu Rev Immunol 18:975–1026

    CAS  PubMed  Google Scholar 

  16. Roark CL et al (2008) gammadelta T cells: an important source of IL-17. Curr Opin Immunol 20(3):353–357

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Pang DJ et al (2012) Understanding the complexity of gammadelta T-cell subsets in mouse and human. Immunology 136(3):283–290

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Chen ZW (2013) Multifunctional immune responses of HMBPP-specific Vgamma2Vdelta2 T cells in M. tuberculosis and other infections. Cell Mol Immunol 10(1):58–64

    PubMed Central  PubMed  Google Scholar 

  19. Kabelitz D, He W (2012) The multifunctionality of human Vgamma9Vdelta2 gammadelta T cells: clonal plasticity or distinct subsets? Scand J Immunol 76(3):213–222

    CAS  PubMed  Google Scholar 

  20. De Rosa SC et al (2004) Ontogeny of gamma delta T cells in humans. J Immunol 172(3):1637–1645

    PubMed  Google Scholar 

  21. O’Leary JJ et al (1988) Expression of the human T cell antigen receptor complex in advanced age. Mech Ageing Dev 45(3):239–252

    PubMed  Google Scholar 

  22. Re F et al (2005) Skewed representation of functionally distinct populations of Vgamma9Vdelta2 T lymphocytes in aging. Exp Gerontol 40(1–2):59–66

    CAS  PubMed  Google Scholar 

  23. Caccamo N et al (2006) Sex-specific phenotypical and functional differences in peripheral human Vgamma9/Vdelta2 T cells. J Leukoc Biol 79(4):663–666

    CAS  PubMed  Google Scholar 

  24. Michishita Y et al (2013) Age-associated alteration of gammadelta T-cell repertoire and different profiles of activation-induced death of Vdelta1 and Vdelta2 T cells. Int J Hematol 94(3):230–240

    Google Scholar 

  25. Roux A et al (2013) Differential impact of age and cytomegalovirus infection on the gammadelta T cell compartment. J Immunol 191(3):1300–1306

    CAS  PubMed  Google Scholar 

  26. Colonna-Romano G et al (2002) Gamma/delta T lymphocytes are affected in the elderly. Exp Gerontol 37(2–3):205–211

    CAS  PubMed  Google Scholar 

  27. Argentati K et al (2002) Numerical and functional alterations of circulating gammadelta T lymphocytes in aged people and centenarians. J Leukoc Biol 72(1):65–71

    CAS  PubMed  Google Scholar 

  28. Hviid L et al (2000) High frequency of circulating gamma delta T cells with dominance of the v(delta)1 subset in a healthy population. Int Immunol 12(6):797–805

    CAS  PubMed  Google Scholar 

  29. Goodier M et al (1993) Gamma delta T cells in the peripheral blood of individuals from an area of holoendemic Plasmodium falciparum transmission. Trans R Soc Trop Med Hyg 87(6):692–696

    CAS  PubMed  Google Scholar 

  30. Cairo C et al (2008) Altered cord blood gammadelta T cell repertoire in Nigeria: possible impacts of environmental factors on neonatal immunity. Mol Immunol 45(11):3190–3197

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Cairo C et al (2010) Impact of age, gender, and race on circulating gammadelta T cells. Hum Immunol 71(10):968–975

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Worku S et al (1997) Higher proportion of CD8+ T cells in the blood in healthy adults from Ethiopia and Bangladesh compared with Sweden. Trans R Soc Trop Med Hyg 91(5):618–622

    CAS  PubMed  Google Scholar 

  33. Polgar B et al (1999) The role of gamma/delta T cell receptor positive cells in pregnancy. Am J Reprod Immunol 41(4):239–244

    CAS  PubMed  Google Scholar 

  34. Zheng NN et al (2011) Association between peripheral gammadelta T-cell profile and disease progression in individuals infected with HIV-1 or HIV-2 in West Africa. J Acquir Immune Defic Syndr 57(2):92–100

    PubMed  Google Scholar 

  35. Poles MA et al (2003) Human immunodeficiency virus type 1 induces persistent changes in mucosal and blood gammadelta T cells despite suppressive therapy. J Virol 77(19):10456–10467

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Rossol R et al (1998) Increase in Vdelta1+ gammadelta T cells in the peripheral blood and bone marrow as a selective feature of HIV-1 but not other virus infections. Br J Haematol 100(4):728–734

    CAS  PubMed  Google Scholar 

  37. Dobmeyer TS et al (2002) Reciprocal alterations of Th1/Th2 function in gammadelta T-cell subsets of human immunodeficiency virus-1-infected patients. Br J Haematol 118(1):282–288

    PubMed  Google Scholar 

  38. Fenoglio D et al (2009) Vdelta1 T lymphocytes producing IFN-gamma and IL-17 are expanded in HIV-1-infected patients and respond to Candida albicans. Blood 113(26):6611–6618

    CAS  PubMed  Google Scholar 

  39. Nilssen DE, Brandtzaeg P (2012) Intraepithelial gammadelta T cells remain increased in the duodenum of AIDS patients despite antiretroviral treatment. PLoS One 7(1):e29066

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Poccia F et al (2009) Zoledronic acid and interleukin-2 treatment improves immunocompetence in HIV-infected persons by activating Vgamma9Vdelta2 T cells. AIDS 23(5):555–565

    CAS  PubMed  Google Scholar 

  41. Ueta C et al (1994) Increase of gamma/delta T cells in hospital workers who are in close contact with tuberculosis patients. Infect Immun 62(12):5434–5441

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Meraviglia S et al (2010) Partial and ineffective activation of V gamma 9V delta 2 T cells by Mycobacterium tuberculosis-infected dendritic cells. J Immunol 185(3):1770–1776

    CAS  PubMed  Google Scholar 

  43. Li B et al (1996) Disease-specific changes in gammadelta T cell repertoire and function in patients with pulmonary tuberculosis. J Immunol 157(9):4222–4229

    CAS  PubMed  Google Scholar 

  44. Gioia C et al (2003) Different cytokine production and effector/memory dynamics of alpha beta+ or gamma delta+ T-cell subsets in the peripheral blood of patients with active pulmonaryA tuberculosis. Int J Immunopathol Pharmacol 16(3):247–252

    CAS  PubMed  Google Scholar 

  45. Szereday L et al (2003) Gamma/delta T cell subsets in patients with active Mycobacterium tuberculosis infection and tuberculin anergy. Clin Exp Immunol 131(2):287–291

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Peng MY et al (2008) Interleukin 17-producing gamma delta T cells increased in patients with active pulmonary tuberculosis. Cell Mol Immunol 5(3):203–208

    PubMed  Google Scholar 

  47. Bourgarit A et al (2009) Tuberculosis-associated immune restoration syndrome in HIV-1-infected patients involves tuberculin-specific CD4 Th1 cells and KIR-negative gammadelta T cells. J Immunol 183(6):3915–3923

    CAS  PubMed  Google Scholar 

  48. Worku S et al (1997) Lymphocyte activation and subset redistribution in the peripheral blood in acute malaria illness: distinct gammadelta+ T cell patterns in Plasmodium falciparum and P. vivax infections. Clin Exp Immunol 108(1):34–41

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Hviid L et al (2001) Perturbation and proinflammatory type activation of V delta 1(+) gamma delta T cells in African children with Plasmodium falciparum malaria. Infect Immun 69(5):3190–3196

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Schwartz E et al (1996) Delayed expansion of V delta 2+ and V delta 1+ gamma delta T cells after acute Plasmodium falciparum and Plasmodium vivax malaria. J Allergy Clin Immunol 97(6):1387–1392

    CAS  PubMed  Google Scholar 

  51. Perera MK et al (1994) Transient increase in circulating gamma/delta T cells during Plasmodium vivax malarial paroxysms. J Exp Med 179(1):311–315

    CAS  PubMed  Google Scholar 

  52. Darabi H et al (2002) Expansion of gammadelta T Cells in patients infected with cutaneous leishmaniasis with and without glucantime therapy. Braz J Infect Dis 6(5):258–262

    PubMed  Google Scholar 

  53. Prigione I et al (2006) T cell mediated immune responses to Toxoplasma gondii in pregnant women with primary toxoplasmosis. Microbes Infect 8(2):552–560

    CAS  PubMed  Google Scholar 

  54. Knight A et al (2010) The role of Vdelta2-negative gammadelta T cells during cytomegalovirus reactivation in recipients of allogeneic stem cell transplantation. Blood 116(12):2164–2172

    CAS  PubMed  Google Scholar 

  55. Couzi L et al (2009) Common features of gammadelta T cells and CD8(+) alphabeta T cells responding to human cytomegalovirus infection in kidney transplant recipients. J Infect Dis 200(9):1415–1424

    CAS  PubMed  Google Scholar 

  56. Dechanet J et al (1999) Implication of gammadelta T cells in the human immune response to cytomegalovirus. J Clin Invest 103(10):1437–1449

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Dechanet J et al (1999) Major expansion of gammadelta T lymphocytes following cytomegalovirus infection in kidney allograft recipients. J Infect Dis 179(1):1–8

    CAS  PubMed  Google Scholar 

  58. Lafarge X et al (2001) Cytomegalovirus infection in transplant recipients resolves when circulating gammadelta T lymphocytes expand, suggesting a protective antiviral role. J Infect Dis 184(5):533–541

    CAS  PubMed  Google Scholar 

  59. Vermijlen D et al (2010) Human cytomegalovirus elicits fetal gammadelta T cell responses in utero. J Exp Med 207(4):807–821

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Pitard V et al (2008) Long-term expansion of effector/memory Vdelta2-gammadelta T cells is a specific blood signature of CMV infection. Blood 112(4):1317–1324

    CAS  PubMed Central  PubMed  Google Scholar 

  61. Macsween KF et al (2010) Infectious mononucleosis in university students in the United kingdom: evaluation of the clinical features and consequences of the disease. Clin Infect Dis 50(5):699–706

    PubMed  Google Scholar 

  62. Hudnall SD et al (2003) Comparative immunophenotypic features of EBV-positive and EBV-negative atypical lymphocytosis. Cytometry B Clin Cytom 55(1):22–28

    PubMed  Google Scholar 

  63. Barcy S et al (2008) Gamma delta+ T cells involvement in viral immune control of chronic human herpesvirus 8 infection. J Immunol 180(5):3417–3425

    CAS  PubMed  Google Scholar 

  64. Aoyagi M et al (2003) Respiratory syncytial virus infection suppresses IFN-gamma production of gammadelta T cells. Clin Exp Immunol 131(2):312–317

    CAS  PubMed Central  PubMed  Google Scholar 

  65. Green S et al (1999) Early CD69 expression on peripheral blood lymphocytes from children with dengue hemorrhagic fever. J Infect Dis 180(5):1429–1435

    CAS  PubMed  Google Scholar 

  66. Hara T et al (1992) Predominant activation and expansion of V gamma 9-bearing gamma delta T cells in vivo as well as in vitro in Salmonella infection. J Clin Invest 90(1):204–210

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Hoshina T et al (2012) NKRP1A+ gammadelta and alphabeta T cells are preferentially induced in patients with Salmonella infection. Hum Immunol 73(6):623–628

    CAS  PubMed  Google Scholar 

  68. Islam D, Christensson B (2000) Disease-dependent changes in T-cell populations in patients with shigellosis. APMIS 108(4):251–260

    CAS  PubMed  Google Scholar 

  69. Schneider T et al (1997) The number and proportion of Vgamma9 Vdelta2 T cells rise significantly in the peripheral blood of patients after the onset of acute Coxiella burnetii infection. Clin Infect Dis 24(2):261–264

    CAS  PubMed  Google Scholar 

  70. Klimpel GR et al (2003) Leptospira interrogans activation of human peripheral blood mononuclear cells: preferential expansion of TCR gamma delta+ T cells vs TCR alpha beta+ T cells. J Immunol 171(3):1447–1455

    CAS  PubMed  Google Scholar 

  71. Jouen-Beades F et al (1997) In vivo and in vitro activation and expansion of gammadelta T cells during Listeria monocytogenes infection in humans. Infect Immun 65(10):4267–4272

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Poquet Y et al (1998) Expansion of Vgamma9 Vdelta2 T cells is triggered by Francisella tularensis-derived phosphoantigens in tularemia but not after tularemia vaccination. Infect Immun 66(5):2107–2114

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Kroca M et al (2000) The proportion of circulating gammadelta T cells increases after the first week of onset of tularaemia and remains elevated for more than a year. Clin Exp Immunol 120(2):280–284

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Kroca M et al (2001) V gamma 9V delta 2 T cells in human legionellosis. Clin Diagn Lab Immunol 8(5):949–954

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Caldwell CW et al (1995) Lymphocytosis of gamma/delta T cells in human ehrlichiosis. Am J Clin Pathol 103(6):761–766

    CAS  PubMed  Google Scholar 

  76. Bertotto A et al (1997) Gamma delta T cells are decreased in the blood of children with Bordetella pertussis infection. Acta Paediatr 86(1):114–115

    CAS  PubMed  Google Scholar 

  77. Watanabe H et al (2000) Psittacosis with increased gammadelta T cells in bronchoalveolar lavage fluid. Respirology 5(2):161–164

    CAS  PubMed  Google Scholar 

  78. Caccamo N et al (2011) Differentiation, phenotype, and function of interleukin-17-producing human Vgamma9Vdelta2 T cells. Blood 118(1):129–138

    CAS  PubMed  Google Scholar 

  79. Bertotto A et al (1993) Lymphocytes bearing the gamma delta T cell receptor in acute Brucella melitensis infection. Eur J Immunol 23(5):1177–1180

    CAS  PubMed  Google Scholar 

  80. Kilic SS et al (2009) Gamma/delta T cells in patients with acute brucellosis. Clin Exp Med 9(2):101–104

    CAS  PubMed  Google Scholar 

  81. Noguchi A et al (2011) Zoledronate-activated Vgamma9gammadelta T cell-based immunotherapy is feasible and restores the impairment of gammadelta T cells in patients with solid tumors. Cytotherapy 13(1):92–97

    CAS  PubMed  Google Scholar 

  82. Bryant NL et al (2009) Characterization and immunotherapeutic potential of gammadelta T-cells in patients with glioblastoma. Neuro Oncol 11(4):357–367

    CAS  PubMed Central  PubMed  Google Scholar 

  83. Bilgi O et al (2008) Peripheral blood gamma-delta T cells in advanced-stage cancer patients. Adv Ther 25(3):218–224

    PubMed  Google Scholar 

  84. Puan KJ et al (2009) Phenotypic and functional alterations of Vgamma2Vdelta2 T cell subsets in patients with active nasopharyngeal carcinoma. Cancer Immunol Immunother 58(7):1095–1107

    CAS  PubMed Central  PubMed  Google Scholar 

  85. Bas M et al (2006) Gamma-delta T-cells in patients with squamous cell carcinoma of the head and neck. Oral Oncol 42(7):691–697

    CAS  PubMed  Google Scholar 

  86. Kuroda H et al (2012) Decreased number and reduced NKG2D expression of Vdelta1 gammadelta T cells are involved in the impaired function of Vdelta1 gammadelta T cells in the tissue of gastric cancer. Gastric Cancer 15(4):433–439

    CAS  PubMed  Google Scholar 

  87. Lee AJ et al (2012) Gammadelta T cells are increased in the peripheral blood of patients with gastric cancer. Clin Chim Acta 413(19–20):1495–1499

    CAS  PubMed  Google Scholar 

  88. Campillo JA et al (2007) Increased number of cytotoxic CD3+ CD28- gammadelta T cells in peripheral blood of patients with cutaneous malignant melanoma. Dermatology 214(4):283–288

    PubMed  Google Scholar 

  89. Provinciali M et al (2010) Persistent ex vivo low number and functional in vitro recovery of circulating gammadelta T cells after removal of a cutaneous primary melanoma. Scand J Immunol 72(2):142–149

    CAS  PubMed  Google Scholar 

  90. Kobayashi H et al (2011) A new indicator of favorable prognosis in locally advanced renal cell carcinomas: gamma delta T-cells in peripheral blood. Anticancer Res 31(3):1027–1031

    PubMed  Google Scholar 

  91. Bennouna J et al (2010) Phase I study of bromohydrin pyrophosphate (BrHPP, IPH 1101), a Vgamma9Vdelta2 T lymphocyte agonist in patients with solid tumors. Cancer Immunol Immunother 59(10):1521–1530

    CAS  PubMed  Google Scholar 

  92. Lang JM et al (2011) Pilot trial of interleukin-2 and zoledronic acid to augment gammadelta T cells as treatment for patients with refractory renal cell carcinoma. Cancer Immunol Immunother 60(10):1447–1460

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Meraviglia S et al (2010) In vivo manipulation of Vgamma9Vdelta2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients. Clin Exp Immunol 161(2):290–297

    CAS  PubMed Central  PubMed  Google Scholar 

  94. Santini D et al (2009) In vivo effects of zoledronic acid on peripheral gammadelta T lymphocytes in early breast cancer patients. Cancer Immunol Immunother 58(1):31–38

    CAS  PubMed  Google Scholar 

  95. Dieli F et al (2007) Targeting human gamma}delta T cells with zoledronate and interleukin-2 for immunotherapy of hormone-refractory prostate cancer. Cancer Res 67(15):7450–7457

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Kobayashi H et al (2007) Safety profile and anti-tumor effects of adoptive immunotherapy using gamma-delta T cells against advanced renal cell carcinoma: a pilot study. Cancer Immunol Immunother 56(4):469–476

    CAS  PubMed  Google Scholar 

  97. Bennouna J et al (2008) Phase-I study of Innacell gammadelta, an autologous cell-therapy product highly enriched in gamma9delta2 T lymphocytes, in combination with IL-2, in patients with metastatic renal cell carcinoma. Cancer Immunol Immunother 57(11):1599–1609

    CAS  PubMed  Google Scholar 

  98. Sakamoto M et al (2011) Adoptive immunotherapy for advanced non-small cell lung cancer using zoledronate-expanded gammadeltaTcells: a phase I clinical study. J Immunother 34(2):202–211

    CAS  PubMed  Google Scholar 

  99. Couzi L et al (2010) Cytomegalovirus-induced gammadelta T cells associate with reduced cancer risk after kidney transplantation. J Am Soc Nephrol 21(1):181–188

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Futagbi G et al (2007) Selective activation of TCR-gammadelta+ cells in endemic Burkitt’s lymphoma. Malar J 6:69

    PubMed Central  PubMed  Google Scholar 

  101. Braza MS et al (2010) Gammadelta T lymphocytes count is normal and expandable in peripheral blood of patients with follicular lymphoma, whereas it is decreased in tumor lymph nodes compared with inflammatory lymph nodes. J Immunol 184(1):134–140

    CAS  PubMed  Google Scholar 

  102. Gertner-Dardenne J et al (2012) Human Vgamma9Vdelta2 T cells specifically recognize and kill acute myeloid leukemic blasts. J Immunol 188(9):4701–4708

    CAS  PubMed  Google Scholar 

  103. Lamb LS Jr et al (1999) Influence of T cell depletion method on circulating gammadelta T cell reconstitution and potential role in the graft-versus-leukemia effect. Cytotherapy 1(1):7–19

    PubMed  Google Scholar 

  104. Godder KT et al (2007) Long term disease-free survival in acute leukemia patients recovering with increased gammadelta T cells after partially mismatched related donor bone marrow transplantation. Bone Marrow Transplant 39(12):751–757

    CAS  PubMed  Google Scholar 

  105. Bank I et al (2003) Expansion of gammadelta T-cells in Behcet’s disease: role of disease activity and microbial flora in oral ulcers. J Lab Clin Med 141(1):33–40

    CAS  PubMed  Google Scholar 

  106. Freysdottir J et al (1999) Gammadelta T cells in Behcet’s disease (BD) and recurrent aphthous stomatitis (RAS). Clin Exp Immunol 118(3):451–457

    CAS  PubMed Central  PubMed  Google Scholar 

  107. Clemente A et al (2010) Phenotype markers and cytokine intracellular production by CD8+ gammadelta T lymphocytes do not support a regulatory T profile in Behcet’s disease patients and healthy controls. Immunol Lett 129(2):57–63

    CAS  PubMed  Google Scholar 

  108. Yamashita N et al (1997) Role of gammadelta T lymphocytes in the development of Behcet’s disease. Clin Exp Immunol 107(2):241–247

    CAS  PubMed Central  PubMed  Google Scholar 

  109. Yasuoka H et al (2008) Preferential activation of circulating CD8+ and gammadelta T cells in patients with active Behcet’s disease and HLA-B51. Clin Exp Rheumatol 26(4 Suppl 50):S59–S63

    CAS  PubMed  Google Scholar 

  110. Direskeneli H et al (2008) Thalidomide has both anti-inflammatory and regulatory effects in Behcet’s disease. Clin Rheumatol 27(3):373–375

    CAS  PubMed  Google Scholar 

  111. Ahn JK et al (2005) Down-regulation of IFN-gamma-producing CD56+ T cells after combined low-dose cyclosporine/prednisone treatment in patients with Behcet’s uveitis. Invest Ophthalmol Vis Sci 46(7):2458–2464

    PubMed  Google Scholar 

  112. Freysdottir J et al (2006) Diversity of gammadelta T cells in patients with Behcet’s disease is indicative of polyclonal activation. Oral Dis 12(3):271–277

    CAS  PubMed  Google Scholar 

  113. Brennan F et al (1989) Coordinate expansion of ‘fetal type’ lymphocytes (TCR gamma delta+ T and CD5+ B) in rheumatoid arthritis and primary Sjogren’s syndrome. Clin Exp Immunol 77(2):175–178

    CAS  PubMed Central  PubMed  Google Scholar 

  114. Kowal-Bielecka O et al (2001) Gamma delta-Lymphocytes in the peripheral blood of patients with rheumatoid arthritis–correlation with clinical and laboratory parameters of the disease and with the treatment used. Rocz Akad Med Bialymst 46:170–181

    CAS  PubMed  Google Scholar 

  115. Smith MD et al (1990) T gamma delta cells and their subsets in blood and synovial tissue from rheumatoid arthritis patients. Scand J Immunol 32(6):585–593

    CAS  PubMed  Google Scholar 

  116. Lunardi C et al (1992) T gamma delta cells and their subsets in blood and synovial fluid from patients with rheumatoid arthritis. Br J Rheumatol 31(8):527–530

    CAS  PubMed  Google Scholar 

  117. Spadaro A et al (2004) Natural killer cells and gamma/delta T cells in synovial fluid and in peripheral blood of patients with psoriatic arthritis. Clin Exp Rheumatol 22(4):389–394

    CAS  PubMed  Google Scholar 

  118. Liu MF et al (1999) Distribution of double-negative (CD4− CD8−, DN) T subsets in blood and synovial fluid from patients with rheumatoid arthritis. Clin Rheumatol 18(3):227–231

    CAS  PubMed  Google Scholar 

  119. Mitogawa T et al (1992) Frequency of gamma delta T cells in peripheral blood, synovial fluid, synovial membrane and lungs from patients with rheumatoid arthritis. Acta Med Okayama 46(5):371–379

    CAS  PubMed  Google Scholar 

  120. Hoshino T et al (1996) TCR gamma delta+ T cells in peripheral blood of patients with adult Still’s disease. J Rheumatol 23(1):124–129

    CAS  PubMed  Google Scholar 

  121. Macaubas C et al (2010) Distribution of circulating cells in systemic juvenile idiopathic arthritis across disease activity states. Clin Immunol 134(2):206–216

    CAS  PubMed Central  PubMed  Google Scholar 

  122. Kenna TJ et al (2012) Enrichment of circulating interleukin-17-secreting interleukin-23 receptor-positive gamma/delta T cells in patients with active ankylosing spondylitis. Arthritis Rheum 64(5):1420–1429

    CAS  PubMed  Google Scholar 

  123. Robak E et al (1999) Circulating TCR gammadelta cells in the patients with systemic lupus erythematosus. Mediators Inflamm 8(6):305–312

    CAS  PubMed Central  PubMed  Google Scholar 

  124. Robak E et al (2001) Lymphocyctes Tgammadelta in clinically normal skin and peripheral blood of patients with systemic lupus erythematosus and their correlation with disease activity. Mediators Inflamm 10(4):179–189

    CAS  PubMed Central  PubMed  Google Scholar 

  125. Wang L et al (2012) Downregulation of CD94/NKG2A inhibitory receptor on decreased gammadelta T cells in patients with systemic lupus erythematosus. Scand J Immunol 76(1):62–69

    CAS  PubMed  Google Scholar 

  126. Li X et al (2011) Generation of human regulatory gammadelta T cells by TCRgammadelta stimulation in the presence of TGF-beta and their involvement in the pathogenesis of systemic lupus erythematosus. J Immunol 186(12):6693–6700

    CAS  PubMed  Google Scholar 

  127. Chauhan SK et al (2006) T-cell receptor repertoire of circulating gamma delta T-cells in Takayasu’s arteritis. Clin Immunol 118(2–3):243–249

    CAS  PubMed  Google Scholar 

  128. Seko Y (2000) Takayasu arteritis: insights into immunopathology. Jpn Heart J 41(1):15–26

    CAS  PubMed  Google Scholar 

  129. Bendersky A et al (2010) Vgamma9+ gammadelta T cells in systemic sclerosis patients are numerically and functionally preserved and induce fibroblast apoptosis. Immunobiology 215(5):380–394

    CAS  PubMed  Google Scholar 

  130. Ueda-Hayakawa I, et al. Circulating gamma/delta T cells in systemic sclerosis exhibit activated phenotype and enhance gene expression of proalpha2(I) collagen of fibroblasts. J Dermatol Sci 69(1):54–60

  131. Riccieri V et al (2005) Reduced circulating natural killer T cells and gamma/delta T cells in patients with systemic sclerosis. J Rheumatol 32(2):283–286

    CAS  PubMed  Google Scholar 

  132. Rinaldi L et al (2006) Longitudinal analysis of immune cell phenotypes in early stage multiple sclerosis: distinctive patterns characterize MRI-active patients. Brain 129(Pt 8):1993–2007

    PubMed  Google Scholar 

  133. Chen Z, Freedman MS (2008) Correlation of specialized CD16(+) gammadelta T cells with disease course and severity in multiple sclerosis. J Neuroimmunol 194(1–2):147–152

    CAS  PubMed  Google Scholar 

  134. Schirmer L et al (2013) Enriched CD161high CCR6+ gammadelta T cells in the cerebrospinal fluid of patients with multiple sclerosis. JAMA Neurol 70(3):345–351

    PubMed  Google Scholar 

  135. Pranzatelli MR et al (2004) Immunophenotype of blood lymphocytes in neuroblastoma-associated opsoclonus-myoclonus. J Pediatr Hematol Oncol 26(11):718–723

    PubMed  Google Scholar 

  136. Pranzatelli MR et al (2004) B- and T-cell markers in opsoclonus-myoclonus syndrome: immunophenoty** of CSF lymphocytes. Neurology 62(9):1526–1532

    CAS  PubMed  Google Scholar 

  137. Scelsa SN et al (2004) Blood gammadelta T cells, Campylobacter jejuni, and GM1 titers in Guillain–Barre syndrome. Muscle Nerve 30(4):423–432

    PubMed  Google Scholar 

  138. Kretowski A et al (2000) Abnormal distribution of gammadelta T lymphocytes in Graves’ disease and insulin-dependent diabetes type 1. Arch Immunol Ther Exp (Warsz) 48(1):39–42

    CAS  Google Scholar 

  139. Toyabe S et al (2001) Oligoclonally expanding gammadelta T lymphocytes induce IgA switching in IgA nephropathy. Clin Exp Immunol 124(1):110–117

    CAS  PubMed Central  PubMed  Google Scholar 

  140. Chen KS et al (1996) Diminution of T cells with gamma delta receptor in the peripheral blood of allergic asthmatic individuals. Clin Exp Allergy 26(3):295–302

    CAS  PubMed  Google Scholar 

  141. Zhao Y et al (2011) Altered expressions of helper T cell (Th)1, Th2, and Th17 cytokines in CD8(+) and gammadelta T cells in patients with allergic asthma. J Asthma 48(5):429–436

    CAS  PubMed  Google Scholar 

  142. Krejsek J et al (1998) Decreased peripheral blood gamma delta T cells in patients with bronchial asthma. Allergy 53(1):73–77

    CAS  PubMed  Google Scholar 

  143. Pons J et al (2005) Blunted gamma delta T-lymphocyte response in chronic obstructive pulmonary disease. Eur Respir J 25(3):441–446

    CAS  PubMed  Google Scholar 

  144. Mota-Pinto A et al (2011) Regulatory T cells in elderly patients with asthma. J Investig Allergol Clin Immunol 21(3):199–206

    CAS  PubMed  Google Scholar 

  145. Schauer U et al (1991) T cell receptor gamma delta bearing cells are decreased in the peripheral blood of patients with atopic diseases. Clin Exp Immunol 86(3):440–443

    CAS  PubMed Central  PubMed  Google Scholar 

  146. Hamzaoui A et al (2002) T cells expressing the gammadelta receptor are essential for Th2-mediated inflammation in patients with acute exacerbation of asthma. Mediators Inflamm 11(2):113–119

    CAS  PubMed Central  PubMed  Google Scholar 

  147. Krug N et al (2001) Cytokine profile of bronchoalveolar lavage-derived CD4(+), CD8(+), and gammadelta T cells in people with asthma after segmental allergen challenge. Am J Respir Cell Mol Biol 25(1):125–131

    CAS  PubMed  Google Scholar 

  148. Spinozzi F et al (1996) Increased allergen-specific, steroid-sensitive gamma delta T cells in bronchoalveolar lavage fluid from patients with asthma. Ann Intern Med 124(2):223–227

    CAS  PubMed  Google Scholar 

  149. Chen M et al (2012) Enhanced peripheral gammadeltaT cells cytotoxicity potential in patients with HBV-associated acute-on-chronic liver failure might contribute to the disease progression. J Clin Immunol 32(4):877–885

    CAS  PubMed  Google Scholar 

  150. Chen M et al (2008) Characteristics of circulating T cell receptor gamma-delta T cells from individuals chronically infected with hepatitis B virus (HBV): an association between V(delta)2 subtype and chronic HBV infection. J Infect Dis 198(11):1643–1650

    PubMed  Google Scholar 

  151. Ferri S et al (2010) A multifaceted imbalance of T cells with regulatory function characterizes type 1 autoimmune hepatitis. Hepatology 52(3):999–1007

    CAS  PubMed  Google Scholar 

  152. Kiyici M et al (2006) Lymphocyte subsets and cytokines in ascitic fluid of decompensated cirrhotic patients with and without spontaneous ascites infection. J Gastroenterol Hepatol 21(6):963–969

    PubMed  Google Scholar 

  153. Fernandez-Ruiz M et al (2009) Pretransplant lymphocyte count predicts the incidence of infection during the first two years after liver transplantation. Liver Transpl 15(10):1209–1216

    PubMed  Google Scholar 

  154. Puig-Pey I et al (2010) Characterization of gammadelta T cell subsets in organ transplantation. Transpl Int 23(10):1045–1055

    CAS  PubMed  Google Scholar 

  155. Andreu-Ballester JC et al (2011) Deficit of gammadelta T lymphocytes in the peripheral blood of patients with Crohn’s disease. Dig Dis Sci 56(9):2613–2622

    PubMed  Google Scholar 

  156. Andreu-Ballester JC et al (2013) Microsporidia and its relation to Crohn’s disease. A retrospective study. PLoS One 8(4):e62107

    CAS  PubMed Central  PubMed  Google Scholar 

  157. Soderstrom K et al (1996) Increased frequency of abnormal gamma delta T cells in blood of patients with inflammatory bowel diseases. J Immunol 156(6):2331–2339

    CAS  PubMed  Google Scholar 

  158. Kelsen J et al (2011) Infliximab induces clonal expansion of gammadelta-T cells in Crohn’s disease: a predictor of lymphoma risk? PLoS One 6(3):e17890

    CAS  PubMed Central  PubMed  Google Scholar 

  159. Kerttula TO et al (1998) Circulating T lymphocyte subsets in coeliac disease (CoD) patients and healthy family members. Clin Exp Immunol 111(3):536–540

    CAS  PubMed Central  PubMed  Google Scholar 

  160. Camarero C et al (2000) Intraepithelial lymphocytes and coeliac disease: permanent changes in CD3−/CD7+ and T cell receptor gammadelta subsets studied by flow cytometry. Acta Paediatr 89(3):285–290

    CAS  PubMed  Google Scholar 

  161. Calleja S et al (2011) Dynamics of non-conventional intraepithelial lymphocytes-NK, NKT, and gammadelta T-in celiac disease: relationship with age, diet, and histopathology. Dig Dis Sci 56(7):2042–2049

    CAS  PubMed  Google Scholar 

  162. Jarvinen TT et al (2003) Intraepithelial lymphocytes in celiac disease. Am J Gastroenterol 98(6):1332–1337

    PubMed  Google Scholar 

  163. Iltanen S et al (1999) Increased density of jejunal gammadelta+ T cells in patients having normal mucosa–marker of operative autoimmune mechanisms? Autoimmunity 29(3):179–187

    CAS  PubMed  Google Scholar 

  164. Torrente F et al (2004) Focal-enhanced gastritis in regressive autism with features distinct from Crohn’s and Helicobacter pylori gastritis. Am J Gastroenterol 99(4):598–605

    PubMed  Google Scholar 

  165. Laggner U et al (2011) Identification of a novel proinflammatory human skin-homing Vgamma9Vdelta2 T cell subset with a potential role in psoriasis. J Immunol 187(5):2783–2793

    CAS  PubMed Central  PubMed  Google Scholar 

  166. Seung NR et al (2007) Comparison of expression of heat-shock protein 60, Toll-like receptors 2 and 4, and T-cell receptor gammadelta in plaque and guttate psoriasis. J Cutan Pathol 34(12):903–911

    PubMed  Google Scholar 

  167. Cai Y et al (2011) Pivotal role of dermal IL-17-producing gammadelta T cells in skin inflammation. Immunity 35(4):596–610

    CAS  PubMed Central  PubMed  Google Scholar 

  168. Cairo C et al (2005) Analysis of circulating gammadelta T cells in children affected by IgE-associated and non-IgE-associated allergic atopic eczema/dermatitis syndrome. Clin Exp Immunol 141(1):116–121

    CAS  PubMed Central  PubMed  Google Scholar 

  169. Katsuta M et al (2006) NK cells and gamma delta+ T cells are phenotypically and functionally defective due to preferential apoptosis in patients with atopic dermatitis. J Immunol 176(12):7736–7744

    CAS  PubMed  Google Scholar 

  170. Moins-Teisserenc HT et al (1999) Association of a syndrome resembling Wegener’s granulomatosis with low surface expression of HLA class-I molecules. Lancet 354(9190):1598–1603

    CAS  PubMed  Google Scholar 

  171. Oswald E et al (2009) Reduced numbers of circulating gammadelta T cells in patients with bullous pemphigoid. Exp Dermatol 18(11):991–993

    PubMed  Google Scholar 

  172. Suzuki S et al (1997) Circadian rhythm of leucocytes and lymphocytes subsets and its possible correlation with the function of the autonomic nervous system. Clin Exp Immunol 110(3):500–508

    CAS  PubMed Central  PubMed  Google Scholar 

  173. Anane LH et al (2010) Phenotypic characterization of gammadelta T cells mobilized in response to acute psychological stress. Brain Behav Immun 24(4):608–614

    CAS  PubMed  Google Scholar 

  174. Atanackovic D et al (2013) Acute psychological stress increases peripheral blood CD3(+)CD56(+) natural killer T cells in healthy men: possible implications for the development and treatment of allergic and autoimmune disorders. Stress 16(4):421–428

    CAS  PubMed  Google Scholar 

  175. Matsushima A et al (2004) Early activation of gammadelta T lymphocytes in patients with severe systemic inflammatory response syndrome. Shock 22(1):11–15

    CAS  PubMed  Google Scholar 

  176. Theodorou GL et al (2007) Effect of non-operative management (NOM) of splenic rupture versus splenectomy on the distribution of peripheral blood lymphocyte populations and cytokine production by T cells. Clin Exp Immunol 150(3):429–436

    CAS  PubMed Central  PubMed  Google Scholar 

  177. Venet F et al (2005) Both percentage of gammadelta T lymphocytes and CD3 expression are reduced during septic shock. Crit Care Med 33(12):2836–2840

    CAS  PubMed  Google Scholar 

  178. Andreu-Ballester JC et al (2013) Association of gammadelta T cells with disease severity and mortality in septic patients. Clin Vaccine Immunol 20(5):738–746

    CAS  PubMed Central  PubMed  Google Scholar 

  179. Niehues T et al (2010) More than just SCID—the phenotypic range of combined immunodeficiencies associated with mutations in the recombinase activating genes (RAG) 1 and 2. Clin Immunol 135(2):183–192

    CAS  PubMed  Google Scholar 

  180. Malan Borel I et al (2003) Gammadelta T cells and interleukin-6 levels could provide information regarding the progression of human renal allograft. Scand J Immunol 58(1):99–105

    CAS  PubMed  Google Scholar 

  181. Yamaguchi T et al (2000) Changes in T-cell receptor subsets after cardiac surgery in children. Surg Today 30(10):875–878

    CAS  PubMed  Google Scholar 

  182. Habermehl P et al (2003) Changes in lymphocyte subsets after cardiac surgery in children. Eur J Pediatr 162(1):15–21

    PubMed  Google Scholar 

  183. Thompson K et al (2011) Fluvastatin does not prevent the acute-phase response to intravenous zoledronic acid in post-menopausal women. Bone 49(1):140–145

    CAS  PubMed  Google Scholar 

  184. Kalyan S et al (2013) Can peripheral blood gammadelta T cells predict osteonecrosis of the jaw? An immunological perspective on the adverse drug-effects of aminobisphosphonate therapy. J Bone Miner Res 28(4):728–735

    CAS  PubMed  Google Scholar 

  185. Matsumoto Y et al (1998) Peripheral deletion of gammadelta T cells in haemodialysis patients. Nephrol Dial Transplant 13(11):2861–2866

    CAS  PubMed  Google Scholar 

  186. Roden AC et al (2008) Immunophenotypic attributes of benign peripheral blood gammadelta T cells and conditions associated with their increase. Arch Pathol Lab Med 132(11):1774–1780

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine F, Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, 52621, Israel

    Ilan Bank & Victoria Marcu-Malina

Authors
  1. Ilan Bank
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Victoria Marcu-Malina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ilan Bank.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bank, I., Marcu-Malina, V. Quantitative Peripheral Blood Perturbations of γδ T Cells in Human Disease and Their Clinical Implications. Clinic Rev Allerg Immunol 47, 311–333 (2014). https://doi.org/10.1007/s12016-013-8391-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-013-8391-x

Keywords

Search

Navigation