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Distributional characteristics of CD25 and CD127 on CD4+ T cell subsets in chronic HCV infection

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Abstract

Attenuated CD4+ T-cell-mediated immune responses are involved in persistence of HCV infection, but the mechanism remains undefined. In this study, the proportions of CD4+ T cell subsets, naïve, central memory, effector memory and effector cells, along with CD25 (IL-2Rα) and CD127 (IL-7Rα) expression on different CD4+ T cell subsets, were measured by polychromatic flow cytometry in 24 chronic HCV-infected individuals and 21 healthy controls. A significant decrease in naïve CD4+ T cells and an increase of central memory and effector memory CD4+ T cells were found in HCV-infected patients compared with healthy controls. HCV-infected patients showed a lower level of CD127 expression in all CD4+ T cells subsets, especially in central memory and effector CD4+ T cells. In terms of total CD4+ T cells, an increase in CD25+ regular T cells (CD4+ CD25+ CD127lo) was found in HCV-infected patients. Interestingly, naïve CD4+ T cells showed increased CD25 expression, while effector memory and effector CD4+ T cells had lower CD25 expression. These data indicated that variations in different fractions of CD4+ T cells, including the phenotypic profile and expression level of CD25 and CD127, may be associated with low efficiency of immune response in chronic HCV infection. These results will strengthen the understanding of pathogenesis and dysfunction of CD4+ T cell immunity during long-term HCV persistence.

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References

  1. Aberle JH, Formann E, Steindl-Munda P, Weseslindtner L, Gurguta C, Perstinger G, Grilnberger E, Laferl H, Dienes HP, Popow-Kraupp T, Ferenci P, Holzmann H (2006) Prospective study of viral clearance and CD4 (+) T-cell response in acute hepatitis C primary infection and reinfection. J Clin Virol 36:24–31

    Article  PubMed  CAS  Google Scholar 

  2. Appasamy PM (1999) Biological and clinical implications of interleukin-7 and lymphopoiesis. Cytokines Cell Mol Ther 5:25–39

    PubMed  CAS  Google Scholar 

  3. Bell JA, Livesey PJ (1985) Cue significance and response regulation in 3- to 6-year-old children’s learning of multiple choice discrimination tasks. Dev Psychobiol 18:229–245

    Article  PubMed  CAS  Google Scholar 

  4. Benbernou N, Muegge K, Durum SK (2000) Interleukin (IL)-7 induces rapid activation of Pyk2, which is bound to Janus kinase 1 and IL-7Ralpha. J Biol Chem 275:7060–7065

    Article  PubMed  CAS  Google Scholar 

  5. Boettler T, Spangenberg HC, Neumann-Haefelin C, Panther E, Urbani S, Ferrari C, Blum HE, von Weizsacker F, Thimme R (2005) T cells with a CD4 + CD25+ regulatory phenotype suppress in vitro proliferation of virus-specific CD8+ T cells during chronic hepatitis C virus infection. J Virol 79:7860–7867

    Article  PubMed  CAS  Google Scholar 

  6. Capa L, Soriano V, Garcia-Samaniego J, Nunez M, Romero M, Cascajero A, Munoz F, Gonzalez-Lahoz J, Benito JM (2007) Influence of HCV genotype and co-infection with human immunodeficiency virus on CD4 (+) and CD8 (+) T-cell responses to hepatitis C virus. J Med Virol 79:503–510

    Article  PubMed  CAS  Google Scholar 

  7. Cerny A, Chisari FV (1999) Pathogenesis of chronic hepatitis C: immunological features of hepatic injury and viral persistence. Hepatology 30:595–601

    Article  PubMed  CAS  Google Scholar 

  8. Cooper S, Erickson AL, Adams EJ, Kansopon J, Weiner AJ, Chien DY, Houghton M, Parham P, Walker CM (1999) Analysis of a successful immune response against hepatitis C virus. Immunity 10:439–449

    Article  PubMed  CAS  Google Scholar 

  9. Dunham RM, Cervasi B, Brenchley JM, Albrecht H, Weintrob A, Sumpter B, Engram J, Gordon S, Klatt NR, Frank I, Sodora DL, Douek DC, Paiardini M, Silvestri G (2008) CD127 and CD25 expression defines CD4+ T cell subsets that are differentially depleted during HIV infection. J Immunol 180:5582–5592

    PubMed  CAS  Google Scholar 

  10. Ebinuma H, Nakamoto N, Li Y, Price DA, Gostick E, Levine BL, Tobias J, Kwok WW, Chang KM (2008) Identification and in vitro expansion of functional antigen-specific CD25 + FoxP3 + regulatory T cells in hepatitis C virus infection. J Virol 82:5043–5053

    Article  PubMed  CAS  Google Scholar 

  11. Erickson AL, Kimura Y, Igarashi S, Eichelberger J, Houghton M, Sidney J, McKinney D, Sette A, Hughes AL, Walker CM (2001) The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes targeted by cytotoxic T lymphocytes. Immunity 15:883–895

    Article  PubMed  CAS  Google Scholar 

  12. Fuller MJ, Hildeman DA, Sabbaj S, Gaddis DE, Tebo AE, Shang L, Goepfert PA, Zajac AJ (2005) Cutting edge: emergence of CD127high functionally competent memory T cells is compromised by high viral loads and inadequate T cell help. J Immunol 174:5926–5930

    PubMed  CAS  Google Scholar 

  13. Gerlach JT, Diepolder HM, Jung MC, Gruener NH, Schraut WW, Zachoval R, Hoffmann R, Schirren CA, Santantonio T, Pape GR (1999) Recurrence of hepatitis C virus after loss of virus-specific CD4(+) T-cell response in acute hepatitis C. Gastroenterology 117:933–941

    Article  PubMed  CAS  Google Scholar 

  14. Golden-Mason L, Burton JR Jr, Castelblanco N, Klarquist J, Benlloch S, Wang C, Rosen HR (2006) Loss of IL-7 receptor alpha-chain (CD127) expression in acute HCV infection associated with viral persistence. Hepatology 44:1098–1109

    Article  PubMed  CAS  Google Scholar 

  15. Grakoui A, Shoukry NH, Woollard DJ, Han JH, Hanson HL, Ghrayeb J, Murthy KK, Rice CM, Walker CM (2003) HCV persistence and immune evasion in the absence of memory T cell help. Science 302:659–662

    Article  PubMed  CAS  Google Scholar 

  16. Grindebacke H, Stenstad H, Quiding-Jarbrink M, Waldenstrom J, Adlerberth I, Wold AE, Rudin A (2009) Dynamic development of homing receptor expression and memory cell differentiation of infant CD4+ CD25high regulatory T cells. J Immunol 183:4360–4370

    Article  PubMed  CAS  Google Scholar 

  17. Gruener NH, Lechner F, Jung MC, Diepolder H, Gerlach T, Lauer G, Walker B, Sullivan J, Phillips R, Pape GR, Klenerman P (2001) Sustained dysfunction of antiviral CD8+ T lymphocytes after infection with hepatitis C virus. J Virol 75:5550–5558

    Article  PubMed  CAS  Google Scholar 

  18. Gruner NH, Gerlach TJ, Jung MC, Diepolder HM, Schirren CA, Schraut WW, Hoffmann R, Zachoval R, Santantonio T, Cucchiarini M, Cerny A, Pape GR (2000) Association of hepatitis C virus-specific CD8+ T cells with viral clearance in acute hepatitis C. J Infect Dis 181:1528–1536

    Article  PubMed  CAS  Google Scholar 

  19. Hazenberg MD, Hamann D, Schuitemaker H, Miedema F (2000) T cell depletion in HIV-1 infection: how CD4+ T cells go out of stock. Nat Immunol 1:285–289

    Article  PubMed  CAS  Google Scholar 

  20. Kaech SM, Wherry EJ, Ahmed R (2002) Effector and memory T-cell differentiation: implications for vaccine development. Nat Rev 2:251–262

    Article  CAS  Google Scholar 

  21. Lechner F, Wong DK, Dunbar PR, Chapman R, Chung RT, Dohrenwend P, Robbins G, Phillips R, Klenerman P, Walker BD (2000) Analysis of successful immune responses in persons infected with hepatitis C virus. J Exp Med 191:1499–1512

    Article  PubMed  CAS  Google Scholar 

  22. Lindenbach BD, Rice CM (2005) Unravelling hepatitis C virus replication from genome to function. Nature 436:933–938

    Article  PubMed  CAS  Google Scholar 

  23. Lucas M, Ulsenheimer A, Pfafferot K, Heeg MH, Gaudieri S, Gruner N, Rauch A, Gerlach JT, Jung MC, Zachoval R, Pape GR, Schraut W, Santantonio T, Nitschko H, Obermeier M, Phillips R, Scriba TJ, Semmo N, Day C, Weber JN, Fidler S, Thimme R, Haberstroh A, Baumert TF, Klenerman P, Diepolder HM (2007) Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection. PloS one 2:e649

    Article  PubMed  CAS  Google Scholar 

  24. Ma A, Koka R, Burkett P (2006) Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Annu Rev Immunol 24:657–679

    Article  PubMed  CAS  Google Scholar 

  25. Maraskovsky E, O’Reilly LA, Teepe M, Corcoran LM, Peschon JJ, Strasser A (1997) Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1−/− mice. Cell 89:1011–1019

    Article  PubMed  CAS  Google Scholar 

  26. McCune JM (2001) The dynamics of CD4+ T-cell depletion in HIV disease. Nature 410:974–979

    Article  PubMed  CAS  Google Scholar 

  27. Missale G, Bertoni R, Lamonaca V, Valli A, Massari M, Mori C, Rumi MG, Houghton M, Fiaccadori F, Ferrari C (1996) Different clinical behaviors of acute hepatitis C virus infection are associated with different vigor of the anti-viral cell-mediated immune response. J Clin Invest 98:706–714

    Article  PubMed  CAS  Google Scholar 

  28. Neumann AU, Lam NP, Dahari H, Gretch DR, Wiley TE, Layden TJ, Perelson AS (1998) Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 282:103–107

    Article  PubMed  CAS  Google Scholar 

  29. Roe B, Coughlan S, Dean J, Lambert JS, Keating S, Norris S, Bergin C, Hall WW (2009) Phenotypic characterization of lymphocytes in HCV/HIV co-infected patients. Viral Immunol 22:39–48

    Article  PubMed  CAS  Google Scholar 

  30. Roifman CM, Zhang J, Chitayat D, Sharfe N (2000) A partial deficiency of interleukin-7R alpha is sufficient to abrogate T-cell development and cause severe combined immunodeficiency. Blood 96:2803–2807

    PubMed  CAS  Google Scholar 

  31. Rushbrook SM, Ward SM, Unitt E, Vowler SL, Lucas M, Klenerman P, Alexander GJ (2005) Regulatory T cells suppress in vitro proliferation of virus-specific CD8+ T cells during persistent hepatitis C virus infection. J Virol 79:7852–7859

    Article  PubMed  CAS  Google Scholar 

  32. Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A (1999) Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401:708–712

    Article  PubMed  CAS  Google Scholar 

  33. Sallusto F, Geginat J, Lanzavecchia A (2004) Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol 22:745–763

    Article  PubMed  CAS  Google Scholar 

  34. Silvestri G, Feinberg MB (2003) Turnover of lymphocytes and conceptual paradigms in HIV infection. J Clin Invest 112:821–824

    PubMed  CAS  Google Scholar 

  35. Stevenson M (2003) HIV-1 pathogenesis. Nat Med 9:853–860

    Article  PubMed  CAS  Google Scholar 

  36. Sugimoto K, Ikeda F, Stadanlick J, Nunes FA, Alter HJ, Chang KM (2003) Suppression of HCV-specific T cells without differential hierarchy demonstrated ex vivo in persistent HCV infection. Hepatology 38:1437–1448

    PubMed  Google Scholar 

  37. Sugimoto K, Stadanlick J, Ikeda F, Brensinger C, Furth EE, Alter HJ, Chang KM (2003) Influence of ethnicity in the outcome of hepatitis C virus infection and cellular immune response. Hepatology 37:590–599

    Article  PubMed  Google Scholar 

  38. Thimme R, Oldach D, Chang KM, Steiger C, Ray SC, Chisari FV (2001) Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med 194:1395–1406

    Article  PubMed  CAS  Google Scholar 

  39. Thimme R, Bukh J, Spangenberg HC, Wieland S, Pemberton J, Steiger C, Govindarajan S, Purcell RH, Chisari FV (2002) Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease. Proc Natl Acad Sci USA 99:15661–15668

    Article  PubMed  CAS  Google Scholar 

  40. Ulsenheimer A, Gerlach JT, Gruener NH, Jung MC, Schirren CA, Schraut W, Zachoval R, Pape GR, Diepolder HM (2003) Detection of functionally altered hepatitis C virus-specific CD4 T cells in acute and chronic hepatitis C. Hepatology 37:1189–1198

    Article  PubMed  Google Scholar 

  41. Venken K, Hellings N, Broekmans T, Hensen K, Rummens JL, Stinissen P (2008) Natural naive CD4 + CD25 + CD127low regulatory T cell (Treg) development and function are disturbed in multiple sclerosis patients: recovery of memory Treg homeostasis during disease progression. J Immunol 180:6411–6420

    PubMed  CAS  Google Scholar 

  42. Ward S, Lauer G, Isba R, Walker B, Klenerman P (2002) Cellular immune responses against hepatitis C virus: the evidence base 2002. Clin Exp Immunol 128:195–203

    Article  PubMed  CAS  Google Scholar 

  43. Wedemeyer H, He XS, Nascimbeni M, Davis AR, Greenberg HB, Hoofnagle JH, Liang TJ, Alter H, Rehermann B (2002) Impaired effector function of hepatitis C virus-specific CD8 + T cells in chronic hepatitis C virus infection. J Immunol 169:3447–3458

    PubMed  CAS  Google Scholar 

  44. Weiss L, Donkova-Petrini V, Caccavelli L, Balbo M, Carbonneil C, Levy Y (2004) Human immunodeficiency virus-driven expansion of CD4 + CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients. Blood 104:3249–3256

    Article  PubMed  CAS  Google Scholar 

  45. Ye SK, Maki K, Kitamura T, Sunaga S, Akashi K, Domen J, Weissman IL, Honjo T, Ikuta K (1999) Induction of germline transcription in the TCRgamma locus by Stat5: implications for accessibility control by the IL-7 receptor. Immunity 11:213–223

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank all participants involved in this study. This work was supported by China National Science and Technology Major Project (2008ZX10002-013) and start-up funds from Peking University Health Science Center (BMU20090529-123).

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Authors and Affiliations

  1. Department of Microbiology, Peking University Health Science Center, 100191, Bei**g, China

    Tao Shen, **angmei Chen, Qiang Xu & Fengmin Lu

  2. Artificial Liver Center, Bei**g You’ an Hospital, Affiliated to Capital Medical University, 100069, Bei**g, China

    Shuang Liu

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Correspondence to Tao Shen or Shuang Liu.

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Shen, T., Chen, X., Xu, Q. et al. Distributional characteristics of CD25 and CD127 on CD4+ T cell subsets in chronic HCV infection. Arch Virol 155, 627–634 (2010). https://doi.org/10.1007/s00705-010-0626-z

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  • DOI: https://doi.org/10.1007/s00705-010-0626-z

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