Heterogeneity in the Differentiation and Function of CD8+ T Cells

Araki K, Turner AP, Shaffer VO et al (2009) mTOR regulates memory CD8 T-cell differentiation. Nature 460:108–112 Beres AJ, Haribhai D, Chadwick AC et al (2012) CD8+ Foxp3+ regulatory T cells are induced during graft-versus-host disease and mitigate disease severity. J Immunol 189:464–474 Billerbeck E, Kang YH, Walker L et al (2010) Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties. Proc Natl Acad Sci USA 107:3006–3011 Buchholz VR, Graf P, Busch DH (2012) The origin of diversity: studying the evolution of multi-faceted CD8+ T cell responses. Cell Mol Life Sci 69:1585–1595 Burrell BE, Csencsits K, Lu G et al (2008) CD8+ Th17 mediate costimulation blockade-resistant allograft rejection in T-bet-deficient mice. J Immunol 181:3906–3914 Cannarile MA, Lind NA, Rivera R et al (2006) Transcriptional regulator Id2 mediates CD8+ T cell immunity. Nat Immunol 7:1317–1325 Cerwenka A, Morgan TM, Harmsen AG et al (1999) Migration kinetics and final destination of type 1 and type 2 CD8 effector cells predict protection against pulmonary virus infection. J Exp Med 189:423–434 Chang SY, Song JH, Guleng B et al (2013) Circulatory antigen processing by mucosal dendritic cells controls CD8(+) T cell activation. Immunity 38:153–165 Cho BA, Sim JH, Park JA et al (2012) Characterization of effector memory CD8+ T cells in the synovial fluid of rheumatoid arthritis. J Clin Immunol 32:709–720 Ciric B, El-behi M, Cabrera R et al (2009) IL-23 drives pathogenic IL-17-producing CD8+ T cells. J Immunol 182:5296–5305 Croft M, Carter L, Swain SL et al (1994) Generation of polarized antigen-specific CD8 effector populations: reciprocal action of interleukin (IL)-4 and IL-12 in promoting type 2 versus type 1 cytokine profiles. J Exp Med 180:1715–1728 Cui W, Liu Y, Weinstein JS et al (2011) An interleukin-21-interleukin-10-STAT3 pathway is critical for functional maturation of memory CD8+ T cells. Immunity 35:792–805 Dusseaux M, Martin E, Serriari N et al (2011) Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells. Blood 117:1250–1259 Endharti AT, Rifa IM, Shi Z et al (2005) Cutting edge: CD8+ CD122+ regulatory T cells produce IL-10 to suppress IFN-gamma production and proliferation of CD8+ T cells. J Immunol 175:7093–7097 Gattinoni L, Klebanoff CA, Restifo NP (2012) Paths to stemness: building the ultimate antitumour T cell. Nat Rev Cancer 12:671–684 Gershon RK, Kondo K (1970) Cell interactions in the induction of tolerance: the role of thymic lymphocytes. Immunology 18:723–737 Grusdat M, McIlwain DR, Xu HC et al (2014) IRF4 and BATF are critical for CD8 T-cell function following infection with LCMV. Cell Death Differ. doi:10.1038/cdd.2014.19 Hamada H, Garcia-Hernandez Mde L, Reome JB et al (2009) Tc17, a unique subset of CD8 T cells that can protect against lethal influenza challenge. J Immunol 182:3469–3481 Hess Michelini R, Doedens AL, Goldrath AW et al (2013) Differentiation of CD8 memory T cells depends on Foxo1. J Exp Med 210:1189–1200 Hinrichs CS, Kaiser A, Paulos CM et al (2009) Type 17 CD8+ T cells display enhanced antitumor immunity. Blood 114:596–599 Hu D, Ikizawa K, Lu L et al (2004) Analysis of regulatory CD8 T cells in Qa-1-deficient mice. Nat Immunol 5:516–523 Huber M, Heink S, Grothe H et al (2009) A Th17-like developmental process leads to CD8(+) Tc17 cells with reduced cytotoxic activity. Eur J Immunol 39:1716–1725 Huber M, Heink S, Pagenstecher A et al (2013) IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis. J Clin Invest 123:247–260 Ichii H, Sakamoto A, Hatano M et al (2002) Role for Bcl-6 in the generation and maintenance of memory CD8+ T cells. Nat Immunol 3:558–563 Intlekofer AM, Takemoto N, Wherry EJ et al (2005) Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. Nat Immunol 6:1236–1244 Intlekofer AM, Banerjee A, Takemoto N et al (2008) Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and eomesodermin. Science 321:408–411 Jeannet G, Boudousquie C, Gardiol N et al (2010) Essential role of the Wnt pathway effector Tcf-1 for the establishment of functional CD8 T cell memory. Proc Natl Acad Sci USA 107:9777–9782 Ji Y, Pos Z, Rao M et al (2011) Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cells. Nat Immunol 12:1230–1237 Jiang H, Canfield SM, Gallagher MP et al (2010) HLA-E-restricted regulatory CD8(+) T cells are involved in development and control of human autoimmune type 1 diabetes. J Clin Invest 120:3641–3650 Joshi NS, Cui W, Chandele A et al (2007) Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor. Immunity 27:281–295 Kaech SM, Cui W (2012) Transcriptional control of effector and memory CD8+ T cell differentiation. Nat Rev Immunol 12:749–761 Kalia V, Sarkar S, Subramaniam S et al (2010) Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo. Immunity 32:91–103 Kallies A, Xin A, Belz GT et al (2009) Blimp-1 transcription factor is required for the differentiation of effector CD8(+) T cells and memory responses. Immunity 31:283–295 Kim HJ, Cantor H (2011) Regulation of self-tolerance by Qa-1-restricted CD8(+) regulatory T cells. Semin Immunol 23:446–452 Kim HJ, Verbinnen B, Tang X et al (2010) Inhibition of follicular T-helper cells by CD8(+) regulatory T cells is essential for self tolerance. Nature 467:328–332 Kim HJ, Wang X, Radfar S et al (2011) CD8 + T regulatory cells express the Ly49 Class I MHC receptor and are defective in autoimmune prone B6-Yaa mice. Proc Natl Acad Sci USA 108:2010–2015 Kim MV, Ouyang W, Liao W et al (2013) The transcription factor Foxo1 controls central-memory CD8+ T cell responses to infection. Immunity 39:286–297 Klenerman P, Hill A (2005) T cells and viral persistence: lessons from diverse infections. Nat Immunol 6:873–879 Kondo T, Takata H, Matsuki F et al (2009) Cutting edge: phenotypic characterization and differentiation of human CD8+ T cells producing IL-17. J Immunol 182:1794–1798 Kryczek I, Bruce AT, Gudjonsson JE et al (2008) Induction of IL-17+ T cell trafficking and development by IFN-gamma: mechanism and pathological relevance in psoriasis. J Immunol 181:4733–4741 Kuang DM, Peng C, Zhao Q et al (2010) Tumor-activated monocytes promote expansion of IL-17-producing CD8 + T cells in hepatocellular carcinoma patients. J Immunol 185:1544–1549 Kurachi M, Barnitz RA, Yosef N et al (2014) The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8 T cells. Nat Immunol 15:373–383 Kuroda S, Yamazaki M, Abe M et al (2011) Basic leucine zipper transcription factor, ATF-like (BATF) regulates epigenetically and energetically effector CD8 T-cell differentiation via Sirt1 expression. Proc Natl Acad Sci USA 108:14885–14889 Le Bourhis L, Mburu YK, Lantz O (2013) MAIT cells, surveyors of a new class of antigen: development and functions. Curr Opin Immunol 25:174–180 Leavenworth JW, Tang X, Kim HJ et al (2013) Amelioration of arthritis through mobilization of peptide-specific CD8+ regulatory T cells. J Clin Invest 123:1382–1389 Loser K, Vogl T, Voskort M et al (2010) The Toll-like receptor 4 ligands Mrp8 and Mrp14 are crucial in the development of autoreactive CD8+ T cells. Nat Med 16:713–717 Lu Y, Hong B, Li H et al (2014) Tumor-specific IL-9-producing CD8+ Tc9 cells are superior effector than type-I cytotoxic Tc1 cells for adoptive immunotherapy of cancers. Proc Natl Acad Sci USA 111:2265–2270 MacIver NJ, Michalek RD, Rathmell JC (2013) Metabolic regulation of T lymphocytes. Annu Rev Immunol 31:259–283 Man K, Miasari M, Shi W et al (2013) The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells. Nat Immunol 14:1155–1165 Marwaha AK, Crome SQ, Panagiotopoulos C et al (2010) Cutting edge: increased IL-17-secreting T cells in children with new-onset type 1 diabetes. J Immunol 185:3814–3818 Nayar R, Enos M, Prince A et al (2012) TCR signaling via Tec kinase ITK and interferon regulatory factor 4 (IRF4) regulates CD8+ T-cell differentiation. Proc Natl Acad Sci USA 109:E2794–E2802 Omori M, Yamashita M, Inami M et al (2003) CD8 T cell-specific downregulation of histone hyperacetylation and gene activation of the IL-4 gene locus by ROG, repressor of GATA. Immunity 19:281–294 Pipkin ME, Sacks JA, Cruz-Guilloty F et al (2010) Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells. Immunity 32:79–90 Raczkowski F, Ritter J, Heesch K et al (2013) The transcription factor interferon regulatory factor 4 is required for the generation of protective effector CD8+ T cells. Proc Natl Acad Sci USA 110:15019–15024 Rangachari M, Mauermann N, Marty RR et al (2006) T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17. J Exp Med 203:2009–2019 Rao RR, Li Q, Odunsi K et al (2010) The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin. Immunity 32:67–78 Rao RR, Li Q, Gubbels Bupp MR et al (2012) Transcription factor Foxo1 represses T-bet-mediated effector functions and promotes memory CD8(+) T cell differentiation. Immunity 36:374–387 Restifo NP, Gattinoni L (2013) Lineage relationship of effector and memory T cells. Curr Opin Immunol 25:556–563 Robb RJ, Lineburg KE, Kuns RD et al (2012) Identification and expansion of highly suppressive CD8(+)FoxP3(+) regulatory T cells after experimental allogeneic bone marrow transplantation. Blood 119:5898–5908 Rutishauser RL, Martins GA, Kalachikov S et al (2009) Transcriptional repressor Blimp-1 promotes CD8(+) T cell terminal differentiation and represses the acquisition of central memory T cell properties. Immunity 31:296–308 Satoh T, Tajima M, Wakita D et al (2012) The development of IL-17/IFN-gamma-double producing CTLs from Tc17 cells is driven by epigenetic suppression of Socs3 gene promoter. Eur J Immunol 42:2329–2342 Saxena A, Desbois S, Carrie N et al (2012) Tc17 CD8+ T cells potentiate Th1-mediated autoimmune diabetes in a mouse model. J Immunol 189:3140–3149 Shrikant PA, Rao R, Li Q et al (2010) Regulating functional cell fates in CD8 T cells. Immunol Res 46:12–22 Smith TR, Kumar V (2008) Revival of CD8+ Treg-mediated suppression. Trends Immunol 29:337–342 Sukumar M, Liu J, Ji Y et al (2013) Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function. J Clin Invest 123:4479–4488 Sun J, Madan R, Karp CL et al (2009) Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nat Med 15:277–284 Sun J, Dodd H, Moser EK et al (2011) CD4+ T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs. Nat Immunol 12:327–334 Tajima M, Wakita D, Noguchi D et al (2008) IL-6-dependent spontaneous proliferation is required for the induction of colitogenic IL-17-producing CD8+ T cells. J Exp Med 205:1019–1027 Takemoto N, Intlekofer AM, Northrup JT et al (2006) Cutting Edge: IL-12 inversely regulates T-bet and eomesodermin expression during pathogen-induced CD8+ T cell differentiation. J Immunol 177:7515–7519 Tang Y, Guan SP, Chua BY et al (2012) Antigen-specific effector CD8 T cells regulate allergic responses via IFN-gamma and dendritic cell function. J Allergy Clin Immunol 129(1611–1620):e4 Tejera MM, Kim EH, Sullivan JA et al (2013) FoxO1 controls effector-to-memory transition and maintenance of functional CD8 T cell memory. J Immunol 191:187–199 Thaventhiran JE, Hoffmann A, Magiera L et al (2012) Activation of the Hippo pathway by CTLA-4 regulates the expression of Blimp-1 in the CD8+ T cell. Proc Natl Acad Sci USA 109:E2223–E2229 Trandem K, Zhao J, Fleming E et al (2011) Highly activated cytotoxic CD8 T cells express protective IL-10 at the peak of coronavirus-induced encephalitis. J Immunol 186:3642–3652 Tsai S, Shameli A, Yamanouchi J et al (2010) Reversal of autoimmunity by boosting memory-like autoregulatory T cells. Immunity 32:568–580 Visekruna A, Ritter J, Scholz T et al (2013) Tc9 cells, a new subset of CD8(+) T cells, support Th2-mediated airway inflammation. Eur J Immunol 43:606–618 Vizler C, Bercovici N, Heurtier A et al (2000) Relative diabetogenic properties of islet-specific Tc1 and Tc2 cells in immunocompetent hosts. J Immunol 165:6314–6321 Walker LJ, Kang YH, Smith MO et al (2012) Human MAIT and CD8alphaalpha cells develop from a pool of type-17 precommitted CD8+ T cells. Blood 119:422–433 Wang R, Green DR (2012) Metabolic checkpoints in activated T cells. Nat Immunol 13:907–915 Wang LX, Li Y, Yang G et al (2010) CD122+ CD8+ Treg suppress vaccine-induced antitumor immune responses in lymphodepleted mice. Eur J Immunol 40:1375–1385 Yang CY, Best JA, Knell J et al (2011) The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets. Nat Immunol 12:1221–1229 Yao S, Buzo BF, Pham D et al (2013) Interferon regulatory factor 4 sustains CD8(+) T cell expansion and effector differentiation. Immunity 39:833–845 Yeh N, Glosson NL, Wang N et al (2010) Tc17 cells are capable of mediating immunity to vaccinia virus by acquisition of a cytotoxic phenotype. J Immunol 185:2089–2098 Yen HR, Harris TJ, Wada S et al (2009) Tc17 CD8 T cells: functional plasticity and subset diversity. J Immunol 183:7161–7168 Yu Y, Cho HI, Wang D et al (2013) Adoptive transfer of Tc1 or Tc17 cells elicits antitumor immunity against established melanoma through distinct mechanisms. J Immunol 190:1873–1881 Zhang N, Bevan MJ (2011) CD8(+) T cells: foot soldiers of the immune system. Immunity 35:161–168 Zhou X, Yu S, Zhao DM et al (2010) Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1. Immunity 33:229–240