Abstract
CD8 positive T cells (CD8 T cells) are immune cells that are crucial in controlling viral infections and the eradication of tumor cells by processes that are primarily dependent on their cytotoxic activities. To exert their effects and due to the consequent strong cytotoxicity, the activation and differentiation of naive CD8 T cells to cytotoxic T lymphocytes (CTLs) are precisely regulated during immune responses. CD8 T cells are primed by antigen-presenting dendritic cells in the presence of permission for activation/differentiation to CTLs. Recent studies have unveiled that Notch signaling gives a license to CD8 T cells to fully activate and become effector cells during priming. In this review, we discuss the recent progresses in the study of the regulation of the activation and function of CD8 T cells by Notch signaling.
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References
Backer RA, Helbig C, Gentek R, Kent A, Laidlaw BJ, Dominguez CX et al (2014) A central role for Notch in effector CD8(+) T cell differentiation. Nat Immunol 15(12):1143–1151
Betjes MG, Meijers RW, de Wit EA, Weimar W, Litjens NH (2012) Terminally differentiated CD8+ Temra cells are associated with the risk for acute kidney allograft rejection. Transplantation 94(1):63–69
Biktasova AK, Dudimah DF, Uzhachenko RV, Park K, Akhter A, Arasada RR et al (2015) Multivalent forms of the Notch Ligand DLL-1 enhance antitumor T-cell immunity in lung cancer and improve efficacy of EGFR-targeted therapy. Cancer Res 75(22):4728–4741
Cho OH, Shin HM, Miele L, Golde TE, Fauq A, Minter LM, et al (2009) Notch regulates cytolytic effector function in CD8+ T cells. J Immunol (Baltimore, Md: 1950) 182(6):3380–3389
Ciofani M, Zuniga-Pflucker JC (2005) Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism. Nat Immunol 6(9):881–888
Doerfler P, Shearman MS, Perlmutter RM (2001) Presenilin-dependent gamma-secretase activity modulates thymocyte development. Proc Natl Acad Sci U S A 98(16):9312–9317
Fowlkes BJ, Robey EA (2002) A reassessment of the effect of activated Notch1 on CD4 and CD8 T cell development. J Immunol (Baltimore, Md: 1950) 169(4):1817–1821
Fu F, Li Y, Qian S, Lu L, Chambers F, Starzl TE et al (1996) Costimulatory molecule-deficient dendritic cell progenitors (MHC class II+, CD80dim, CD86-) prolong cardiac allograft survival in nonimmunosuppressed recipients. Transplantation 62(5):659–665
Gimmi CD, Freeman GJ, Gribben JG, Gray G, Nadler LM (1993) Human T-cell clonal anergy is induced by antigen presentation in the absence of B7 costimulation. Proc Natl Acad Sci U S A 90(14):6586–6590
Glimcher LH, Townsend MJ, Sullivan BM, Lord GM (2004) Recent developments in the transcriptional regulation of cytolytic effector cells. Nat Rev Immunol 4(11):900–911
Hadland BK, Manley NR, Su D, Longmore GD, Moore CL, Wolfe MS et al (2001) Gamma -secretase inhibitors repress thymocyte development. Proc Natl Acad Sci U S A 98(13):7487–7491
Haque M, Song J, Fino K, Sandhu P, Wang Y, Ni B et al (2016) Melanoma immunotherapy in mice using genetically engineered pluripotent stem cells. Cell Transplant 25(5):811–827
Hu W, Lu C, Dong HH, Huang J, Shen DY, Stone RL et al (2011) Biological roles of the Delta family Notch ligand Dll4 in tumor and endothelial cells in ovarian cancer. Cancer Res 71(18):6030–6039
Kaech SM, Cui W (2012) Transcriptional control of effector and memory CD8+ T cell differentiation. Nat Rev Immunol 12(11):749–761
Kijima M, Iwata A, Maekawa Y, Uehara H, Izumi K, Kitamura A, et al (2009) Jagged1 suppresses collagen-induced arthritis by indirectly providing a negative signal in CD8+ T cells. J Immunol (Baltimore, Md:1950) 182(6):3566–3572
Kijima M, Yamaguchi T, Ishifune C, Maekawa Y, Koyanagi A, Yagita H et al (2008) Dendritic cell-mediated NK cell activation is controlled by Jagged2-Notch interaction. Proc Natl Acad Sci U S A 105(19):7010–7015
Kuijk LM, Verstege MI, Rekers NV, Bruijns SC, Hooijberg E, Roep BO et al (2013) Notch controls generation and function of human effector CD8+ T cells. Blood 121(14):2638–2646
Li GG, Li L, Li C, Ye LY, Li XW, Liu DR et al (2013) Influence of up-regulation of Notch ligand DLL4 on biological behaviors of human gastric cancer cells. World J Gastroenterol 19(28):4486–4494
Maekawa Y, Ishifune C, Tsukumo S, Hozumi K, Yagita H, Yasutomo K (2015) Notch controls the survival of memory CD4+ T cells by regulating glucose uptake. Nat Med 21(1):55–61
Maekawa Y, Minato Y, Ishifune C, Kurihara T, Kitamura A, Kojima H et al (2008) Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity. Nat Immunol 9(10):1140–1147
Mathieu M, Cotta-Grand N, Daudelin JF, Thebault P, Labrecque N (2013) Notch signaling regulates PD-1 expression during CD8(+) T-cell activation. Immunol Cell Biol 91(1):82–88
Mathieu M, Duval F, Daudelin JF, Labrecque N (2015) The Notch signaling pathway controls short-lived effector CD8+ T cell differentiation but is dispensable for memory generation. J Immunol (Baltimore, Md: 1950) 194(12):5654–5662
McAdam AJ, Schweitzer AN, Sharpe AH (1998) The role of B7 co-stimulation in activation and differentiation of CD4+ and CD8+ T cells. Immunol Rev 165:231–247
Mescher MF, Agarwal P, Casey KA, Hammerbeck CD, **ao Z, Curtsinger JM (2007) Molecular basis for checkpoints in the CD8 T cell response: tolerance versus activation. Semin Immunol 19(3):153–161
Okamoto M, Takeda K, Joetham A, Ohnishi H, Matsuda H, Swasey CH et al (2008) Essential role of Notch signaling in effector memory CD8+ T cell-mediated airway hyperresponsiveness and inflammation. J Exp Med 205(5):1087–1097
Palaga T, Miele L, Golde TE, Osborne BA (2003) TCR-mediated Notch signaling regulates proliferation and IFN-gamma production in peripheral T cells. J Immunol (Baltimore, Md : 1950) 171(6):3019–3024
Priyadharshini B, Greiner DL, Brehm MA (2012) T-cell activation and transplantation tolerance. Transplant Rev 26(3):212–222
Pui JC, Allman D, Xu L, DeRocco S, Karnell FG, Bakkour S et al (1999) Notch1 expression in early lymphopoiesis influences B versus T lineage determination. Immunity 11(3):299–308
Purow BW, Haque RM, Noel MW, Su Q, Burdick MJ, Lee J et al (2005) Expression of Notch-1 and its ligands, Delta-like-1 and Jagged-1, is critical for glioma cell survival and proliferation. Cancer Res 65(6):2353–2363
Radtke F, Wilson A, Stark G, Bauer M, van Meerwijk J, MacDonald HR et al (1999) Deficient T cell fate specification in mice with an induced inactivation of Notch1. Immunity 10(5):547–558
Robey E, Chang D, Itano A, Cado D, Alexander H, Lans D et al (1996) An activated form of Notch influences the choice between CD4 and CD8 T cell lineages. Cell 87(3):483–492
Sandy AR, Chung J, Toubai T, Shan GT, Tran IT, Friedman A, et al (2013) T cell-specific notch inhibition blocks graft-versus-host disease by inducing a hyporesponsive program in alloreactive CD4+ and CD8+ T cells. J Immunol (Baltimore Md: 1950) 190(11):5818–5828
Sierra RA, Thevenot P, Raber PL, Cui Y, Parsons C, Ochoa AC et al (2014) Rescue of notch-1 signaling in antigen-specific CD8+ T cells overcomes tumor-induced T-cell suppression and enhances immunotherapy in cancer. Cancer Immunol Res 2(8):800–811
St. Louis JD, Lederer JA, Lichtman AH (1993) Costimulator deficient antigen presentation by an endothelial cell line induces a nonproliferative T cell activation response without anergy. J Exp Med 178(5):1597–1605
Sugimoto K, Maekawa Y, Kitamura A, Nishida J, Koyanagi A, Yagita H, et al (2010) Notch2 signaling is required for potent antitumor immunity in vivo. J Immunol (BaltimoreMd: 1950) 184(9):4673–4678
Tanigaki K, Tsuji M, Yamamoto N, Han H, Tsukada J, Inoue H et al (2004) Regulation of alphabeta/gammadelta T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling. Immunity 20(5):611–622
Williams MA, Bevan MJ (2007) Effector and memory CTL differentiation. Annu Rev Immunol 25:171–192
Wolfer A, Bakker T, Wilson A, Nicolas M, Ioannidis V, Littman DR et al (2001) Inactivation of Notch 1 in immature thymocytes does not perturb CD4 or CD8T cell development. Nat Immunol 2(3):235–241
Wong KK, Carpenter MJ, Young LL, Walker SJ, McKenzie G, Rust AJ et al (2003) Notch ligation by Delta1 inhibits peripheral immune responses to transplantation antigens by a CD8+ cell-dependent mechanism. J Clin Invest 112(11):1741–1750
Yamada Y, Boskovic S, Aoyama A, Murakami T, Putheti P, Smith RN et al (2012) Overcoming memory T-cell responses for induction of delayed tolerance in nonhuman primates. Am J Transplant 12(2):330–340
Yap M, Brouard S, Pecqueur C, Degauque N (2015) Targeting CD8 T-Cell Metabolism in Transplantation. Front Immunol 6:547
Yasutomo K, Doyle C, Miele L, Fuchs C, Germain RN (2000) The duration of antigen receptor signalling determines CD4+ versus CD8+ T-cell lineage fate. Nature 404(6777):506–510
Zhao E, Maj T, Kryczek I, Li W, Wu K, Zhao L et al (2016) Cancer mediates effector T cell dysfunction by targeting microRNAs and EZH2 via glycolysis restriction. Nat Immunol 17(1):95–103
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Maekawa, Y., Ikeda, T., Srinontong, P. (2017). Notch Controls the Differentiation and Function of Cytotoxic CD8 T Cells. In: Yasutomo, K. (eds) Notch Signaling. Springer, Singapore. https://doi.org/10.1007/978-981-10-4971-2_2
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DOI: https://doi.org/10.1007/978-981-10-4971-2_2
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