CD8⁺ T regulatory/suppressor cells and their relationships with autoreactivity and autoimmunity

References

• Gershon RK, Kondo K. Infectious immunological tolerance. Immunology. 1971; 21:903–914.
   PubMed Web of Science ®Google Scholar
• Moller G. Do suppressor T cells exist?. Scand J Immunol. 1988; 27:247–250.
   PubMed Web of Science ®Google Scholar
• Sakaguchi S. Regulatory T cells: Key controllers of immunologic self-tolerance. Cell. 2000; 101:455–458.
   PubMed Web of Science ®Google Scholar
• Bouneaud C, Kourilsky P, Bousso P. Impact of negative selection on the T cell clonal deletion. Immunity. 2000; 13:829–840.
   PubMed Web of Science ®Google Scholar
• Moudgil KD, Sercarz EE. The self-directed T cell repertoire: Its creation and activation. Rev Immunogenetics. 2000; 2:26–37.
   PubMedGoogle Scholar
• Maverakis E, van den Elzen P, Sercarz EE. Self-reactive T cells and degeneracy of T cell recognition: Evolving concepts-from sequence homology to shape mimicry and TCR flexibility. J Autoimmun. 2001; 16:201–209.
   Google Scholar
• Matzinger P. Tolerance, danger and the extended family. Annu Rev Immunol. 1994; 12:991–1045.
   PubMed Web of Science ®Google Scholar
• Konya C, Goronzy JJ, Weyand CM. Treating autoimmune disease by targeting CD8+ T suppressor cells. Expert Opin Biol Ther. 2009; 9:951–965.
   PubMed Web of Science ®Google Scholar
• Smith TRF, Kumar V. Revival of CD8+ Treg mediated suppression. Trends Immunol. 2008; 29:337–342.
   PubMed Web of Science ®Google Scholar
• Cosmi L, Liotta F, Lazzeri E, Francalanci M, Angeli R, Mazzinghi B, Santarlasci V, Manetti R, Vanini V, Romagnani P, Maggi E, Romagnani S, Annunziato F. Human CD8+ CD25+ thymocytes share phenotypic and functional features with CD4+ CD25+ regulatory thymocytes. Blood. 2003; 102:4107–4114.
   PubMed Web of Science ®Google Scholar
• Maggi E, Cosmi L, Liotta F, Romagnani P, Romagnani S, Annunziato F. Thymic regulatory T cells. Autoimmun Rev. 2005; 4:579–586.
   PubMed Web of Science ®Google Scholar
• Bienvenu B, Martin B, Auffray C, Cordier C, Bécourt C, Lucas B. Peripheral CD8+ CD25+ T lymphocytes from MHC class II-deficient mice exhibit regulatory activity. J Immunol. 2005; 175:246–253.
   PubMed Web of Science ®Google Scholar
• Endharti AT, Rifa'I M, Shi Z, Fukuoka Y, Nakahara Y, Kawamoto Y, Takeda K, Isobe K, Suzuki H. Cutting edge: CD8+ CD122+ regulatory T cells produce IL-10 to suppress IFN-γ production and proliferation of CD8+ T cells. J Immunol. 2005; 175:7093–7097.
   PubMed Web of Science ®Google Scholar
• Rifa'i M, Shi Z, Zhang SY, Lee YH, Shiku H, Isobe K, Suzuki H. CD8+ CD122+ regulatory T cells recognize activated T cells via conventional MHC class I-αβ TCR interaction and become IL-10-producing active regulatory cells. Int Immunol. 2008; 20:937–947.
   PubMed Web of Science ®Google Scholar
• Miyara M, Sakaguchi S. Natural regulatory T cells: Mechanisms of suppression. Trends Mol Med. 2007; 13:108–116.
   PubMed Web of Science ®Google Scholar
• Jiang H, Braunstein NS, Yu B, Winchester R, Chess L. CD8+ T cells control the Th phenotype of MBP-reactive CD4+ T cells in EAE mice. Proc Natl Acad Sci USA. 2001; 98:6301–6316.
   PubMed Web of Science ®Google Scholar
• Feger U, Tolosa E, Huang Y-H, Waschbisch A, Biedermann T, Melms A, Wiendl H. HLA-G expression defines a novel regulatory T cell subset present in human peripheral blood and sites of inflammation. Blood. 2007; 110:568–577.
   PubMed Web of Science ®Google Scholar
• Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008; 133:775–787.
   PubMed Web of Science ®Google Scholar
• Jiang H, Chess L. Qa-1/HLA-E-restricted regulatory CD8+ T cells and self-nonself discrimination: An essay on peripheral T-cell regulation. Hum Immunol. 2008; 69:721–727.
   Google Scholar
• Fontenot JD, Rasmussen JP, Gavin MA, Rudensky AY. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol. 2005; 6:1142–1151.
   PubMed Web of Science ®Google Scholar
• Bautista JL, Lio CW, Lathrop SK, Forbush K, Liang Y, Luo J, Rudensky AY, Hsieh CS. Intraclonal competition limits the fate determination of regulatory T cells in the thymus. Nat Immunol. 2009; 10:610–617.
   PubMed Web of Science ®Google Scholar
• Qin H, Vlad G, Cortesini R, Suciu-Foca N, Manavalan JS. CD8+ suppressor and cytotoxic T cells recognize the same human leukocyte antigen-A2 restricted cytomegalovirus peptide. Hum Immunol. 2008; 69:776–780.
   Google Scholar
• Rifa'i M, Kawamoto Y, Nakashima I, Suzuki H. Essential roles for CD8+ CD122+ regulatory T cells in the maintenance of T cell homeostasis. J Exp Med. 2004; 200:1123–1134.
   PubMed Web of Science ®Google Scholar
• Lee YH, Ishida Y, Rifa'i M, Shi Z, Isobe K, Suzuki H. Essential roles for CD8+ CD122+ regulatory T cells in the recovery from experimental autoimmune encephalomyelitis. J Immunol. 2008; 180:825–832.
   PubMed Web of Science ®Google Scholar
• Rubtsov YP, Rasmussen JP, Chi EY, Fontenot J, Castelli L, Ye X, Treuting P, Siewe L, Roers A, Henderson WRJr, Muller W, Rudensky AY. Regulatory T cell derived interleukin-10 limits inflammation at environmental interfaces. Immunity. 2008; 28:546–558.
   PubMed Web of Science ®Google Scholar
• Filaci G, Fravega M, Negrini S, Procopio F, Fenoglio D, Rizzi M, Brenci S, Contini P, Olive D, Ghio M, Setti M, Accolla RS, Puppo F, Indiveri F. Non-antigen specific CD8+ T suppressor lymphocytes originate from CD8+ CD28+ T cells and inhibit both T cell proliferation and CTL function. Hum Immunol. 2004; 65:142–156.
   PubMed Web of Science ®Google Scholar
• Suzuki M, Konya C, Goronzy JJ, Weyand CM. Inhibitory CD8+ T cells in autoimmune disease. Hum Immunol. 2008; 69:781–789.
   PubMed Web of Science ®Google Scholar
• Mahic M, Henjum K, Yakub S, Bjornbeth BA, Torgersen KM, Tasken K, Aandahl EM. Generation of highly suppressive adaptive CD8+ CD25+ FOXP3+ regulatory T cells by continuous antigen stimulation. Eur J Immunol. 2008; 38:640–646.
   PubMed Web of Science ®Google Scholar
• Ben-David H, Sharabi A, Dayan M, Sela M, Mozes E. The role of CD8+ CD28 − regulatory cells in suppressing myasthenia gravis-associated responses by a dual altered peptide ligand. Proc Natl Acad Sci USA. 2007; 104:17459–17464.
   PubMed Web of Science ®Google Scholar
• Ciubotariu R, Colovai AI, Pennesi G, Liu Z, Smith D, Berlocco P, Cortesini R, Suciu-Foca N. Specific suppression of human CD4+ Th cell responses to pig MHC antigens by CD8+ CD28 − regulatory T cells. J Immunol. 1998; 161:5193–5202.
   PubMed Web of Science ®Google Scholar
• Jarvis LB, Matyszak MK, Duggleby RC, Goodall JC, Hall FC, Gaston JS. Autoreactive human peripheral blood CD8+ T cells with a regulatory phenotype and function. Eur J Immunol. 2005; 35:2896–2908.
   PubMed Web of Science ®Google Scholar
• Singh RR. SLE: Translating lessons from models system to human disease. Trends Immunol. 2005; 26:572–579.
   Google Scholar
• Brusko TM, Putnam AL, Bluestone JA. Human regulatory T cells: Role in autoimmune disease and therapeutic opportunities. Immunol Rev. 2008; 223:371–390.
   PubMed Web of Science ®Google Scholar
• Filaci G, Bacilieri S, Fravega M, Monetti M, Contini P, Ghio M, Setti M, Puppo F, Indiveri F. Impairment of CD8+ T suppressor cell function in patients with active systemic lupus erythematosus. J Immunol. 2001; 166:6452–6457.
   PubMed Web of Science ®Google Scholar
• Crispin JC, Martinez A, Alcocer-Varela J. Quantification of regulatory T cells in patients with systemic lupus erythematosus. J Autoimmun. 2003; 21:273–276.
   PubMed Web of Science ®Google Scholar
• Miyara M, Amoura Z, Parizot C, Badoual C, Dorgham K, Trad S, Nochy D, Debré P, Piette JC, Gorochov G. Global natural regulatory T cell depletion in active systemic lupus erythematosus. J Immunol. 2005; 175:8392–8400.
   PubMed Web of Science ®Google Scholar
• Valencia X, Yarboro C, Illei G, Lipsky PE. Deficient CD4+ CD25high T regulatory cell function in patients with active systemic lupus erythematosus. J Immunol. 2007; 178:2579–2588.
   PubMed Web of Science ®Google Scholar
• Venigalla RK, Tretter T, Krienke S, Max R, Eckstein V, Blank N, Fiehn C, Ho AD, Lorenz HM. Reduced CD4+, CD25 − T cell sensitivity to the suppressive function of CD4+, CD25high, CD127 − /low regulatory T cells in patients with active systemic lupus erythematosus. Arthritis Rheum. 2008; 58:2120–2130.
   PubMed Web of Science ®Google Scholar
• Singh RP, Hahn BH, La Cava A. Tuning immune suppression in systemic autoimmunity with self-derived peptides. Inflamm Allergy Drug Targets. 2008; 7:253–259.
   Google Scholar
• La Cava A, Ebling FM, Hahn BH. Ig-Reactive CD4+ CD25+ T cells from tolerized (New Zealand Black x New Zealand White)F1 mice suppress in vitro production of antibodies to DNA. J Immunol. 2004; 173:3542–3548.
   PubMed Web of Science ®Google Scholar
• Hahn BH, Singh RP, La Cava A, Ebling FM. Tolerogenic treatment of lupus mice with consensus peptide induces Foxp3-expressing, apoptosis-resistant, TGFβ secreting CD8+ T cell suppressors. J Immunol. 2005; 175:7728–7737.
   PubMed Web of Science ®Google Scholar
• Skaggs BJ, Singh RP, Hahn BH. Induction of immune tolerance by activation of CD8+ T suppressor/regulatory cells in lupus-prone mice. Hum Immunol. 2008; 69:790–796.
   Google Scholar
• Kang HK, Michaels MA, Berner BR, Datta SK. Very low-dose tolerance with nucleosomal peptides controls lupus and induces potent regulatory T cell subsets. J Immunol. 2005; 174:3247–3255.
   PubMed Web of Science ®Google Scholar
• van Amelsfort JM, Jacobs KM, Bijlsma JW, Lafeber FP, Taams LS. CD4+ CD25+ regulatory T cells in rheumatoid arthritis: Differences in the presence, phenotype, and function between peripheral blood and synovial fluid. Arthritis Rheum. 2004; 50:2775–2785.
   PubMed Web of Science ®Google Scholar
• Cao D, van Vollenhoven R, Klareskog L, Trollmo C, Malmstrom V. CD25 brightCD41 regulatory T cells are enriched in inflamed joints of patients with chronic rheumatic disease. Arthritis Res Ther. 2004; 6:R335–R346.
   PubMedGoogle Scholar
• Mottonen M, Helkkinen J, Mustonen L, Isomaki P, Luukkainen R, Lassila O. CD4+ CD25+ T cells with the phenotypic and functional characteristics of regulatory T cells are enriched in the synovial fluid of patients with rheumatoid arthritis. Clin Exp Immunol. 2005; 140:360–367.
   PubMed Web of Science ®Google Scholar
• Klimiuk PA, Goronzy JJ, Weyand CM. IL-16 as an anti-inflammatory cytokine in rheumatoid synovitis. J Immunol. 1999; 162:4293–4299.
   PubMed Web of Science ®Google Scholar
• Davila E, Kang YM, Park YW, Sawai H, He X, Pryshchep S, Goronzy JJ, Weyand CM. Cell-based immunotherapy with suppressor CD8+ T cells in rheumatoid arthritis. J Immunol. 2005; 174:7292–7301.
   PubMed Web of Science ®Google Scholar
• Seo SK, Choi JH, Kim YH, Kang WJ, Park HY, Suh JH, Choi BK, Vinay DS, Kwon BS. 4-1BB-mediated immunotherapy of rheumatoid arthritis. Nat Med. 2004; 10:1088–1094.
   PubMed Web of Science ®Google Scholar
• Balashov KE, Khoury SJ, Hafler DA, Weiner HL. Inhibition of T cell responses by activated human CD8+ T cells is mediated by interferon-γ and is defective in chronic progressive multiple sclerosis. J Clin Invest. 1995; 95:2711–2719.
   PubMed Web of Science ®Google Scholar
• Tennakoon DK, Mehta RS, Ortega SB, Bhoj V, Racke MK, Karandikar NJ. Therapeutic induction of regulatory, cytotoxic CD8+ T cells in multiple sclerosis. J Immunol. 2006; 176:7119–7129.
   PubMed Web of Science ®Google Scholar
• Villa Correale J. Isolation and characterization of CD8+ regulatory T cells in multiple sclerosis. J Neuroimmunol. 2008; 195:121–134.
   Google Scholar
• Biegler BW, Yan SX, Ortega SB, Tennakoon DK, Racke MK, Karandikar NJ. Glatiramer acetate (GA) therapy induces a focused, oligoclonal CD8+ T-cell repertoire in multiple sclerosis. J Neuroimmunol. 2006; 180:159–171.
   PubMedGoogle Scholar
• Huang YH, Zozulya AL, Weidenfeller C, Metz I, Buck D, Toyka KV, Brück W, Wiendl H. Specific central nervous system recruitment of HLA-G+ regulatory T cells in multiple sclerosis. Ann Neurol. 2009; 66:171–183.
   PubMed Web of Science ®Google Scholar
• Jiang H, Zhang SI, Pernis B. Role of CD8+ T cells in murine experimental allergic encephalomyelitis. Science. 1992; 256:1213–1215.
   PubMed Web of Science ®Google Scholar
• Montero E, Nussbaum G, Kaye JF, Perez R, Lage A, Ben-Nun A, Cohen IR. Regulation of experimental autoimmune encephalomyelitis by CD4+, CD25+ and CD8+ T cells: Analysis using depleting antibodies. J Autoimmun. 2004; 23:1–7.
   PubMedGoogle Scholar
• Hu D, Ikizawa K, Lu L, Sanchirico ME, Shinohara ML, Cantor H. Analysis of regulatory CD8 T cells in Qa-1-deficient mice. Nat Immunol. 2004; 5:516–523.
   PubMed Web of Science ®Google Scholar
• Miller A, Lider O, Roberts AB, Sporn MB, Weiner HL. Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor β after antigen-specific triggering. Proc Natl Acad Sci USA. 1992; 89:21–435.
   Google Scholar
• Bisikirska B, Colgan J, Luban J, Bluestone JA, Herold KC. TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+ CD25+ Tregs. J Clin Invest. 2005; 115:2904–2913.
   PubMed Web of Science ®Google Scholar
• Wang R, Han G, Song L, Wang J, Chen G, Xu R, Yu M, Qian J, Shen B, Li Y. CD8+ regulatory T cells are responsible for GAD-IgG gene-transferred tolerance induction in NOD mice. Immunology. 2009; 126:123–131.
   PubMed Web of Science ®Google Scholar
• Filaci G, Fravega M, Fenoglio D, Rizzi M, Negrini S, Viggiani R, Indiveri F. Non-antigen specific CD8+ T suppressor lymphocytes. Clin Exp Med. 2004; 4:86–92.
   PubMed Web of Science ®Google Scholar
• Filaci G, Rizzi M, Setti M, Fenoglio D, Fravega M, Basso M, Ansaldo G, Ceppa P, Borgonovo G, Murdaca G, Ferrera F, Picciotto A, Fiocca R, Torre G, Indiveri F. Non-antigen-specific CD8+ T suppressor lymphocytes in diseases characterized by chronic immune responses and inflammation. Ann N Y Acad Sci. 2005; 1050:115–123.
   PubMed Web of Science ®Google Scholar
• Saitoh O, Abiru N, Nakahara M, Nagayama Y. CD8+CD122+ T cells, a newly identified regulatory T subset, negatively regulate Graves’ hyperthyroidism in a murine model. Endocrinology. 2007; 148:6040–6046.
   PubMed Web of Science ®Google Scholar
• Zhang L, Jarvis LB, Baek HJ, Gaton JS. Regulatory IL4+ CD8+ T cells in patients with ankylosng spondylitis and healthy controls. Ann Rheum Dis. 2009; 68:1345–1351.
   Google Scholar
• Choi BK, Asai T, Vinay DS, Kim YH, Kwon BS. 4-1BB-mediated amelioration of experimental autoimmune uveoretinitis is caused by indoeamine 2,3-dioxygenase-dependent mechanisms. Cyokine. 2006; 34:233–242.
   PubMed Web of Science ®Google Scholar
• Vlad G, Coresini R, Suciu-Foca N. CD8+ T suppressor cells and the ILT3 master switch. Hum Immunol. 2008; 69:681–686.
   PubMed Web of Science ®Google Scholar
• Uss E, Rowshani AT, Hooibrink B, Lardy NM, van Lier RA, ten Berge I. CD103 is a marker for alloantigen-induced regulatory CD8+ T cells. J Immunol. 2006; 177:2775–2783.
   PubMed Web of Science ®Google Scholar
• Gilliet M, Liu YJ. Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells. J Exp Med. 2002; 195:695–704.
   PubMed Web of Science ®Google Scholar
• Wei S, Kryczek I, Zou L, Daniel B, Cheng P, Mottram P, Curiel T, Lange A, Zou W. Plasmacytoid dendritic cells induce CD8+ regulatory T cells in human ovarian carcinoma. Cancer Res. 2005; 65:5020–5026.
   PubMed Web of Science ®Google Scholar
• Gray JD, Hirokawa M, Ohtsuka K, Horwitz DA. Generation of an inhibitory circuit involving CD8+ T cells, IL-2, and NK cell-derived TGF-β: Contrasting effects of anti-CD2 and anti-CD3. J Immunol. 1998; 160:2248–2254.
   Google Scholar
• Billerbeck E, Blum HE, Thimme R. Parallel expansion of human virus-specific FoxP3 − effector memory and de novo-generated FoxP3+ regulatory CD8+ T cells upon antigen recognition in vitro. J Immunol. 2007; 179:1039–1048.
   Google Scholar
• Joosten SA, van Meijgaarden KE, Savage ND, de Boer T, Triebel F, van der Wal A, de Heer E, Klein MR, Geluk A, Ottenhoff TH. Identification of a human CD8+ regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4. Proc Natl Acad Sci USA. 2007; 104:8029–8034.
   PubMed Web of Science ®Google Scholar
• Ménager-Marcq I, Pomié C, Romagnoli P, van Meerwijk JP. CD8+ CD28 − regulatory T lymphocytes prevent experimental inflammatory bowel disease in mice. Gastroenterology. 2006; 131:1775–1785.
   PubMed Web of Science ®Google Scholar
• Zheng SG, Wang JH, Koss MN, Quismorio FJr, Gray JD, Horwitz DA. CD4+ and CD8+ regulatory T cells generated ex vivo with IL-2 and TGF-β suppress a stimulatory graft-versus-host disease with a lupus-like syndrome. J Immunol. 2004; 172:1531–1539.
   PubMed Web of Science ®Google Scholar
• Allez M, Brimnes J, Dotan I, Mayer L. Expansion of CD8+ T cells with regulatory function after interaction with intestinal epithelial cells. Gastroenterology. 2002; 123:1516–1526.
   PubMed Web of Science ®Google Scholar
• Ho J, Kurtz CC, Naganuma M, Ernst PB, Cominelli F, Rivera-Nieves J. A CD8+/CD103high T cell subset regulates TNF-mediated chronic murine ileitis. J Immunol. 2008; 180:2573–2580.
   PubMed Web of Science ®Google Scholar
• Izawa A, Yamaura K, Albin MJ, Jurewicz M, Tanaka K, Clarkson MR, Ueno T, Habicht A, Freeman GJ, Yagita H, Abdi R, Pearson T, Greiner DL, Sayegh MH, Najafian N. A novel alloantigen-specific CD8+ PD1+ regulatory T cell induced by ICOS-B7h blockade in vivo. J Immunol. 2007; 179:786–796.
   Google Scholar
• Najafian N, Chitnis T, Salama AD, Zhu B, Benou C, Yuan X, Clarkson MR, Sayegh MH, Khoury SJ. Regulatory functions of CD8+ CD28 − T cells in an autoimmune disease model. J Clin Invest. 2003; 112:1037–1048.
   PubMed Web of Science ®Google Scholar