CD8 + Tregs in autoimmunity: Learning "self"-control from experience

Cellular and Molecular Life Sciences

Volumn 68, Issue 23, 2011, Pages 3781-3795

  Tsai, Sue ^a   Clemente Casares, Xavier ^a   Santamaria, Pere ^a,b  

^a UNIVERSITY OF CALGARY   (Canada)

^b UNIVERSITY OF CALGARY   (Canada)

Author keywords

Autoimmunity; CD8 + regulatory T cells; Immune response; Memory like phenotype; T cell memory

Indexed keywords

CD103 ANTIGEN; CD28 ANTIGEN; CD45RO ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GAMMA INTERFERON; GLATIRAMER; GLYCOPROTEIN P 15095; HLA DQA1 ANTIGEN; HLA E ANTIGEN; HLA G ANTIGEN; INTERLEUKIN 10; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 2 RECEPTOR BETA; MYELIN BASIC PROTEIN; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA;

ALLERGIC ENCEPHALOMYELITIS; ANTIGEN SPECIFICITY; AUTOIMMUNE DISEASE; AUTOIMMUNITY; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CYTOKINE RELEASE; ENTERITIS; HUMAN; IMMUNOREGULATION; INSULIN DEPENDENT DIABETES MELLITUS; LONG TERM EXPOSURE; LYMPHOCYTE DIFFERENTIATION; MEMORY T LYMPHOCYTE; MULTIPLE SCLEROSIS; MYASTHENIA GRAVIS; NEGATIVE FEEDBACK; NONHUMAN; REGULATORY T LYMPHOCYTE; REVIEW; RHEUMATOID ARTHRITIS; SYSTEMIC LUPUS ERYTHEMATOSUS; T LYMPHOCYTE ACTIVATION;

ANIMALS; AUTOIMMUNITY; CD8-POSITIVE T-LYMPHOCYTES; HUMANS; T-LYMPHOCYTES, REGULATORY;

EID: 82255163008     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-011-0738-y     Document Type: Review

References (135)

1. Gershon RK, Cohen P, Hencin R, Liebhaber SA (1972) Suppressor T cells. J Immunol 108(3):586-590
2. Gershon RK, Kondo K (1970) Cell interactions in the induction of tolerance: the role of thymic lymphocytes. Immunology 18(5):723-737
3. Gershon RK, Kondo K (1971) Infectious immunological tolerance. Immunology 21(6):903-914
4. Cantor H, Hugenberger J, McVay-Boudreau L, Eardley DD, Kemp J, Shen FW, Gershon RK (1978) Immunoregulatory circuits among T-cell sets. Identification of a subpopulation of T-helper cells that induces feedback inhibition. J Exp Med 148(4):871-877 (Pubitemid 9034256)
5. Cantor H, Shen FW, Boyse EA (1976) Separation of helper T cells from suppressor T cells expressing different Ly components, II. Activation by antigen: after immunization, antigenspecific suppressor and helper activities are mediated by distinct T-cell subclasses. J Exp Med 143(6):1391-1340
6. Eardley DD, Hugenberger J, McVay-Boudreau L, Shen FW, Gershon RK, Cantor H (1978) Immunoregulatory circuits among T-cell sets. I. T-helper cells induce other T-cell sets to exert feedback inhibition. J Exp Med 147(4):1106-1115 (Pubitemid 8318079)
7. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M (1995) Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155(3):1151-1164
8. Bluestone JA, Abbas AK (2003) Natural versus adaptive regulatory T cells. Nat Rev Immunol 3(3):253-257 (Pubitemid 37323210)
9. Jordan MS, Boesteanu A, Reed AJ, Petrone AL, Holenbeck AE, Lerman MA, Naji A, Caton AJ (2001) Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist selfpeptide. Nat Immunol 2(4):301-306 (Pubitemid 33706340)
10. Picca CC, Larkin J 3rd, Boesteanu A, Lerman MA, Rankin AL, Caton AJ (2006) Role of TCR specificity in CD4+CD25+ regulatory T-cell selection. Immunol Rev 212:74-85 (Pubitemid 44116701)
11. Lio CW, Hsieh CS (2008) A two-step process for thymic regulatory T cell development. Immunity 28(1):100-111
12. Bettini ML, Vignali DA (2010) Development of thymically derived natural regulatory T cells. Ann N Y Acad Sci 1183:1-12
13. Roncarolo MG, Bacchetta R, Bordignon C, Narula S, Levings MK (2001) Type 1 T regulatory cells. Immunol Rev 182:68-79 (Pubitemid 33070208)
14. Faria AM, Weiner HL (2006) Oral tolerance and TGF-betaproducing cells. Inflamm Allergy Drug Targets 5(3):179-190
15. Vignali DA, Collison LW, Workman CJ (2008) How regulatory T cells work. Nat Rev Immunol 8(7):523-532
16. Goverman J, Perchellet A, Huseby ES (2005) The role of CD8(+) T cells in multiple sclerosis and its animal models. Curr Drug Targets Inflamm Allergy 4 (2):239-245 (Pubitemid 40873106)
17. Tsai S, Shameli A, Santamaria P (2008) CD8+ T cells in type 1 diabetes. Adv Immunol 100:79-124
18. Walter U, Santamaria P (2005) CD8+ T cells in autoimmunity. Curr Opin Immunol 17(6):624-631
19. Balashov KE, Khoury SJ, Hafler DA, Weiner HL (1995) Inhibition of T cell responses by activated human CD8+ T cells is mediated by interferon-gamma and is defective in chronic progressive multiple sclerosis. J Clin Invest 95(6):2711-2719
20. Filaci G, Bacilieri S, Fravega M, Monetti M, Contini P, Ghio M, Setti M, Puppo F, Indiveri F (2001) Impairment of CD8+ T suppressor cell function in patients with active systemic lupus erythematosus. J Immunol 166(10):6452-6457 (Pubitemid 32440781)
21. Mikulkova Z, Praksova P, Stourac P, Bednarik J, Strajtova L, Pacasova R, Belobradkova J, Dite P, Michalek J (2010) Numerical defects in CD8+ CD28-T-suppressor lymphocyte population in patients with type 1 diabetes mellitus and multiple sclerosis. Cell Immunol 262(2):75-79
22. Singh RP, Hahn BH, La Cava A (2008) Tuning immune suppression in systemic autoimmunity with self-derived peptides. Inflamm Allergy Drug Targets 7(4):253-259
23. Biegler BW, Yan SX, Ortega SB, Tennakoon DK, Racke MK, Karandikar NJ (2006) Glatiramer acetate (GA) therapy induces a focused, oligoclonal CD8+ T-cell repertoire in multiple sclerosis. J Neuroimmunol 180(1-2):159-171 (Pubitemid 44692328)
24. Choi BK, Asai T, Vinay DS, Kim YH, Kwon BS (2006) 4-1BB-mediated amelioration of experimental autoimmune uveoretinitis is caused by indoleamine 2, 3-dioxygenase-dependent mechanisms. Cytokine 34(5-6):233-242 (Pubitemid 44224104)
25. Hahn BH, Singh RP, La Cava A, Ebling FM (2005) Tolerogenic treatment of lupus mice with consensus peptide induces Foxp3-expressing, apoptosis-resistant, TGFbeta-secreting CD8+ T cell suppressors. J Immunol 175(11):7728-7737 (Pubitemid 41713473)
26. Jiang H, Kashleva H, Xu LX, Forman J, Flaherty L, Pernis B, Braunstein NS, Chess L (1998) T cell vaccination induces T cell receptor Vbeta-specific Qa-1-restricted regulatory CD8(+) T cells. Proc Natl Acad Sci USA 95 (8):4533-4537 (Pubitemid 28207947)
27. Kang HK, Michaels MA, Berner BR, Datta SK (2005) Very low-dose tolerance with nucleosomal peptides controls lupus and induces potent regulatory T cell subsets. J Immunol 174(6):3247-3255 (Pubitemid 40354027)
28. Seo SK, Choi JH, Kim YH, Kang WJ, Park HY, Suh JH, Choi BK, Vinay DS, Kwon BS (2004) 4-1BB-mediated immunotherapy of rheumatoid arthritis. Nat Med 10(10):1088-1094 (Pubitemid 39424870)
29. Skaggs BJ, Singh RP, Hahn BH (2008) Induction of immune tolerance by activation of CD8+ T suppressor/regulatory cells in lupus-prone mice. Hum Immunol 69(11):790-796
30. Tang X, Maricic I, Kumar V (2007) Anti-TCR antibody treatment activates a novel population of nonintestinal CD8 alpha alpha + TCR alpha beta + regulatory T cells and prevents experimental autoimmune encephalomyelitis. J Immunol 178(10):6043-6050 (Pubitemid 46717383)
31. Tennakoon DK, Mehta RS, Ortega SB, Bhoj V, Racke MK, Karandikar NJ (2006) Therapeutic induction of regulatory, cytotoxic CD8+ T cells in multiple sclerosis. J Immunol 176(11):7119-7129 (Pubitemid 43787894)
32. Tsai S, Shameli A, Yamanouchi J, Clemente-Casares X, Wang J, Serra P, Yang Y, Medarova Z, Moore A, Santamaria P (2010) Reversal of autoimmunity by boosting memory-like autoregulatory T cells. Immunity 32(4):568-580
33. Wang R, Han G, Song L, Wang J, Chen G, Xu R, Yu M, Qian J, Shen B, Li Y (2009) CD8+ regulatory T cells are responsible for GAD-IgG gene-transferred tolerance induction in NOD mice. Immunology 126(1):123-131
34. Hu D, Ikizawa K, Lu L, Sanchirico ME, Shinohara ML, Cantor H (2004) Analysis of regulatory CD8 T cells in Qa-1-deficient mice. Nat Immunol 5(5):516-523 (Pubitemid 38660464)
35. Gaur A, Ruberti G, Haspel R, Mayer JP, Fathman CG (1993) Requirement for CD8+ cells in T cell receptor peptide-induced clonal unresponsiveness. Science 259(5091):91-94 (Pubitemid 23036093)
36. Panoutsakopoulou V, Huster KM, McCarty N, Feinberg E, Wang R, Wucherpfennig KW, Cantor H (2004) Suppression of autoimmune disease after vaccination with autoreactive T cells that express Qa-1 peptide complexes. J Clin Invest 113(8):1218-1224 (Pubitemid 38544107)
37. Beeston T, Smith TR, Maricic I, Tang X, Kumar V (2010) Involvement of IFN-gamma and perforin, but not Fas/FasL interactions in regulatory T cell-mediated suppression of experimental autoimmune encephalomyelitis. J Neuroimmunol 229(1-2):91-97
38. Jiang H, Chess L (2000) The specific regulation of immune responses by CD8+ T cells restricted by the MHC class Ib molecule, Qa-1. Annu Rev Immunol 18:185-216 (Pubitemid 30365379)
39. Madakamutil LT, Maricic I, Sercarz E, Kumar V (2003) Regulatory T cells control autoimmunity in vivo by inducing apoptotic depletion of activated pathogenic lymphocytes. J Immunol 170(6):2985-2992 (Pubitemid 36302171)
40. Tang X, Maricic I, Purohit N, Bakamjian B, Reed-Loisel LM, Beeston T, Jensen P, Kumar V (2006) Regulation of immunity by a novel population of Qa-1-restricted CD8alphaalpha + TCRalphabeta + T cells. J Immunol 177(11):7645-7655 (Pubitemid 44846279)
41. Kim HJ, Verbinnen B, Tang X, Lu L, Cantor H (2010) Inhibition of follicular T-helper cells by CD8(+) regulatory T cells is essential for self tolerance. Nature 467 (7313):328-332
42. Chen W, Zhang L, Liang B, Saenger Y, Li J, Chess L, Jiang H (2007) Perceiving the avidity of T cell activation can be translated into peripheral T cell regulation. Proc Natl Acad Sci USA 104(51):20472-20477
43. Jiang H (2005) The Qa-1 dependent CD8+ T cell mediated regulatory pathway. Cell Mol Immunol 2(3):161-167
44. Jiang H, Canfield SM, Gallagher MP, Jiang HH, Jiang Y, Zheng Z, Chess L (2010) HLA-E-restricted regulatory CD8(+) T cells are involved in development and control of human autoimmune type 1 diabetes. J Clin Invest 120 (10):3641-3650
45. Shmidt TE, Zhuchenko TD, Iakhno NN (2003) Glatiramer acetate (Copaxone) influence on different stages of multiple sclerosis pathogenesis. Zh Nevrol Psikhiatr Im S S Korsakova (Spec No 2): 79-82
46. Yamada H, Matsuzaki G, Iwamoto Y, Nomoto K (2000) Unusual cytotoxic activities of thymus-independent, self-antigenspecific CD8(+) T cells. Int Immunol 12 (12):1677-1683 (Pubitemid 32040843)
47. Yamada H, Matsuzaki G, Chen Q, Iwamoto Y, Nomoto K (2001) Reevaluation of the origin of CD44(high) "memory phenotype" CD8 T cells: comparison between memory CD8 T cells and thymus-independent CD8 T cells. Eur J Immunol 31 (6):1917-1926 (Pubitemid 32547353)
48. Suzuki H, Kundig TM, Furlonger C, Wakeham A, Timms E, Matsuyama T, Schmits R, Simard JJ, Ohashi PS, Griesser H, et al. (1995) Deregulated T cell activation and autoimmunity in mice lacking interleukin-2 receptor beta. Science 268(5216):1472-1476
49. Rifa'i M, Kawamoto Y, Nakashima I, Suzuki H (2004) Essential roles of CD8+CD122+ regulatory T cells in the maintenance of T cell homeostasis. J Exp Med 200(9):1123-1134 (Pubitemid 39507052)
50. Endharti AT, Rifa IM, Shi Z, Fukuoka Y, Nakahara Y, Kawamoto Y, Takeda K, Isobe K, Suzuki H (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(11):7093-7097 (Pubitemid 41713400)
51. Shi Z, Rifa'i M, Lee YH, Shiku H, Isobe K, Suzuki H (2008) Importance of CD80/CD86-CD28 interactions in the recognition of target cells by CD8+CD122+ regulatory T cells. Immunology 124(1):121-128 (Pubitemid 351537579)
52. Dai H, Wan N, Zhang S, Moore Y, Wan F, Dai Z (2010) Cutting edge: programmed death-1 defines CD8+CD122+ T cells as regulatory versus memory T cells. J Immunol 185(2):803-807
53. Saitoh O, Abiru N, Nakahara M, Nagayama Y (2007) CD8+CD122+ T cells, a newly identified regulatory T subset, negatively regulate Graves' hyperthyroidism in a murine model. Endocrinology 148(12):6040-6046 (Pubitemid 350146196)
54. Lee YH, Ishida Y, Rifa'i M, Shi Z, Isobe K, Suzuki H (2008) Essential role of CD8+CD122+ regulatory T cells in the recovery from experimental autoimmune encephalomyelitis. J Immunol 180(2):825-832
55. Endharti AT, Okuno Y, Shi Z, Misawa N, Toyokuni S, Ito M, Isobe K, Suzuki H (2011) CD8+CD122+ regulatory T Cells (Tregs) and CD4+ Tregs cooperatively prevent and cure CD4+ cell-induced colitis. J Immunol 186(1):41-52
56. Shi Z, Okuno Y, Rifa'i M, Endharti AT, Akane K, Isobe K, Suzuki H (2009) Human CD8+CXCR3+T cells have the same function as murine CD8+CD122+Treg. Eur J Immunol 39(8):2106-2119
57. Liu Z, Tugulea S, Cortesini R, Suciu-Foca N (1998) Specific suppression of T helper alloreactivity by allo-MHC class I-restricted CD8+CD28-T cells. Int Immunol 10(6):775-783 (Pubitemid 28279480)
58. Ciubotariu R, Colovai AI, Pennesi G, Liu Z, Smith D, Berlocco P, Cortesini R, Suciu-Foca N (1998) Specific suppression of human CD4+ Th cell responses to pig MHC antigens by CD8+CD28-regulatory T cells. J Immunol 161(10):5193-5202 (Pubitemid 28519077)
59. Colovai AI, Liu Z, Ciubotariu R, Lederman S, Cortesini R, Suciu-Foca N (2000) Induction of xenoreactive CD4+ T-cell anergy by suppressor CD8+CD28-T cells. Transplantation 69(7):1304-1310 (Pubitemid 30238715)
60. Jiang S, Tugulea S, Pennesi G, Liu Z, Mulder A, Lederman S, Harris P, Cortesini R, Suciu-Foca N (1998) Induction of MHC-class I restricted human suppressor T cells by peptide priming in vitro. Hum Immunol 59(11):690-699 (Pubitemid 28467718)
61. Scotto L, Naiyer AJ, Galluzzo S, Rossi P, Manavalan JS, Kim-Schulze S, Fang J, Favera RD, Cortesini R, Suciu-Foca N (2004) Overlap between molecular markers expressed by naturally occurring CD4+CD25+ regulatory T cells and antigen specific CD4+CD25+ and CD8+CD28-T suppressor cells. Hum Immunol 65(11):1297-1306 (Pubitemid 39535293)
62. Chang CC, Ciubotariu R, Manavalan JS, Yuan J, Colovai AI, Piazza F, Lederman S, Colonna M, Cortesini R, Dalla-Favera R, Suciu-Foca N (2002) Tolerization of dendritic cells by T (S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat Immunol 3(3):237-243 (Pubitemid 34218114)
63. Manavalan JS, Kim-Schulze S, Scotto L, Naiyer AJ, Vlad G, Colombo PC, Marboe C, Mancini D, Cortesini R, Suciu-Foca N (2004) Alloantigen specific CD8+CD28-FOXP3+ T suppressor cells induce ILT3+ILT4+ tolerogenic endothelial cells, inhibiting alloreactivity. Int Immunol 16(8):1055-1068 (Pubitemid 39136723)
64. Kim-Schulze S, Scotto L, Vlad G, Piazza F, Lin H, Liu Z, Cortesini R, Suciu-Foca N (2006) Recombinant Ig-like transcript 3-Fc modulates T cell responses via induction of Th anergy and differentiation of CD8+ T suppressor cells. J Immunol 176(5):2790-2798
65. Najafian N, Chitnis T, Salama AD, Zhu B, Benou C, Yuan X, Clarkson MR, Sayegh MH, Khoury SJ (2003) Regulatory functions of CD8+CD28-T cells in an autoimmune disease model. J Clin Invest 112(7):1037-1048 (Pubitemid 38056319)
66. Ben-David H, Sharabi A, Dayan M, Sela M, Mozes E (2007) The role of CD8+CD28 regulatory cells in suppressing myasthenia gravis-associated responses by a dual altered peptide ligand. Proc Natl Acad Sci USA 104(44):17459-17464 (Pubitemid 350219860)
67. Paas-Rozner M, Dayan M, Paas Y, Changeux JP, Wirguin I, Sela M, Mozes E (2000) Oral administration of a dual analog of two myasthenogenic T cell epitopes down-regulates experimental autoimmune myasthenia gravis in mice. Proc Natl Acad Sci USA 97(5):2168-2173 (Pubitemid 30134040)
68. Davila E, Kang YM, Park YW, Sawai H, He X, Pryshchep S, Goronzy JJ, Weyand CM (2005) Cell-based immunotherapy with suppressor CD8+ T cells in rheumatoid arthritis. J Immunol 174(11):7292-7301 (Pubitemid 40705699)
69. 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 (2005) Non-antigenspecific CD8 (+) T suppressor lymphocytes in diseases characterized by chronic immune responses and inflammation. Ann N Y Acad Sci 1050:115-123 (Pubitemid 41129428)
70. Crucian B, Dunne P, Friedman H, Ragsdale R, Pross S, Widen R (1995) Alterations in levels of CD28-/CD8+ suppressor cell precursor and CD45RO+/CD4+ memory T lymphocytes in the peripheral blood of multiple sclerosis patients. Clin Diagn Lab Immunol 2(2):249-252
71. 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 (2004) Nonantigen specific CD8+ T suppressor lymphocytes originate from CD8+CD28-T cells and inhibit both T-cell proliferation and CTL function. Hum Immunol 65(2):142-156 (Pubitemid 38224140)
72. Picker LJ, Terstappen LW, Rott LS, Streeter PR, Stein H, Butcher EC (1990) Differential expression of homing-associated adhesion molecules by T cell subsets in man. J Immunol 145(10):3247-3255
73. Hadley GA, Bartlett ST, Via CS, Rostapshova EA, Moainie S (1997) The epithelial cell-specific integrin, CD103(alpha E integrin), defines a novel subset of alloreactive CD8+CTL. J Immunol 159 (8):3748-3756 (Pubitemid 127469629)
74. Wang D, Yuan R, Feng Y, El-Asady R, Farber DL, Gress RE, Lucas PJ, Hadley GA (2004) Regulation of CD103 expression by CD8+ T cells responding to renal allografts. J Immunol 172(1):214-221 (Pubitemid 38020474)
75. El-Asady R, Yuan R, Liu K, Wang D, Gress RE, Lucas PJ, Drachenberg CB, Hadley GA (2005) TGF-{beta}-dependent CD103 expression by CD8(+) T cells promotes selective destruction of the host intestinal epithelium during graft-versushost disease. J Exp Med 201 (10):1647-1657 (Pubitemid 40721008)
76. Hadley GA, Charandee C, Weir MR, Wang D, Bartlett ST, Drachenberg CB (2001) CD103+CTL accumulate within the graft epithelium during clinical renal allograft rejection. Transplantation 72(9):1548-1555 (Pubitemid 33095514)
77. Uss E, Rowshani AT, Hooibrink B, Lardy NM, van Lier RA, ten Berge IJ (2006) CD103 is a marker for alloantigen-induced regulatory CD8+ T cells. J Immunol 177(5):2775-2783 (Pubitemid 44277792)
78. Koch SD, Uss E, van Lier RA, ten Berge IJ (2008) Alloantigeninduced regulatory CD8+CD103+ T cells. Hum Immunol 69(11):737-744
79. Myers L, Croft M, Kwon BS, Mittler RS, Vella AT (2005) Peptide-specific CD8 T regulatory cells use IFN-gamma to elaborate TGF-beta-based suppression. J Immunol 174(12):7625-7632 (Pubitemid 40806267)
80. Ho J, Kurtz CC, Naganuma M, Ernst PB, Cominelli F, Rivera-Nieves J (2008) A CD8+/CD103high T cell subset regulates TNF-mediated chronic murine ileitis. J Immunol 180(4):2573-2580
81. Lu L, Yu Y, Li G, Pu L, Zhang F, Zheng S, Wang X (2009) CD8(+) CD103 (+) regulatory T cells in spontaneous tolerance of liver allografts. Int Immunopharmacol 9 (5):546-548
82. Le Gal FA, Riteau B, Sedlik C, Khalil-Daher I, Menier C, Dausset J, Guillet JG, Carosella ED, Rouas-Freiss N (1999) HLA-G-mediated inhibition of antigen-specific cytotoxic T lymphocytes. Int Immunol 11(8):1351-1356 (Pubitemid 29355674)
83. Lila N, Rouas-Freiss N, Dausset J, Carpentier A, Carosella ED (2001) Soluble HLA-G protein secreted by allo-specific CD4+ T cells suppresses the allo-proliferative response: a CD4+ T cell regulatory mechanism. Proc Natl Acad Sci USA 98(21):12150-12155 (Pubitemid 32959842)
84. Riteau B, Menier C, Khalil-Daher I, Sedlik C, Dausset J, Rouas-Freiss N, Carosella ED (1999) HLA-G inhibits the allogeneic proliferative response. J Reprod Immunol 43(2):203-211 (Pubitemid 29349684)
85. Feger U, Tolosa E, Huang YH, Waschbisch A, Biedermann T, Melms A, Wiendl H (2007) HLA-G expression defines a novel regulatory T-cell subset present in human peripheral blood and sites of inflammation. Blood 110(2):568-577 (Pubitemid 47105395)
86. Huang YH, Zozulya AL, Weidenfeller C, Metz I, Buck D, Toyka KV, Bruck W, Wiendl H (2009) Specific central nervous system recruitment of HLA-G (+) regulatory T cells in multiple sclerosis. Ann Neurol 66(2):171-183
87. 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 (2003) Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes. Blood 102(12):4107-4114 (Pubitemid 37486995)
88. Prevosto C, Zancolli M, Canevali P, Zocchi MR, Poggi A (2007) Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction. Haematologica 92(7):881-888 (Pubitemid 350144234)
89. 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 (2007) Identification of a human CD8+ regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4. Proc Natl Acad Sci USA 104(19):8029-8034 (Pubitemid 47185870)
90. Mahic M, Henjum K, Yaqub S, Bjornbeth BA, Torgersen KM, Tasken K, Aandahl EM (2008) Generation of highly suppressive adaptive CD8(+) CD25 (+) FOXP3 (+) regulatory T cells by continuous antigen stimulation. Eur J Immunol 38 (3):640-646
91. Jarvis LB, Matyszak MK, Duggleby RC, Goodall JC, Hall FC, Gaston JS (2005) Autoreactive human peripheral blood CD8+ T cells with a regulatory phenotype and function. Eur J Immunol 35(10):2896-2908 (Pubitemid 41555085)
92. Bisikirska B, Colgan J, Luban J, Bluestone JA, Herold KC (2005) TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs. J Clin Invest 115(10):2904-2913 (Pubitemid 41434418)
93. Correale J, Villa A (2010) Role of CD8 + CD25 + Foxp3 + regulatory T cells in multiple sclerosis. Ann Neurol 67(5):625-368
94. Bienvenu B, Martin B, Auffray C, Cordier C, Becourt C, Lucas B (2005) Peripheral CD8+CD25+ T lymphocytes from MHC class II-deficient mice exhibit regulatory activity. J Immunol 175(1):246-253 (Pubitemid 40884325)
95. Westendorf AM, Fleissner D, Deppenmeier S, Gruber AD, Bruder D, Hansen W, Liblau R, Buer J (2006) Autoimmunemediated intestinal inflammation-impact and regulation of antigen-specific CD8+ T cells. Gastroenterology 131(2):510-524 (Pubitemid 44142451)
96. Fleissner D, Hansen W, Geffers R, Buer J, Westendorf AM (2010) Local induction of immunosuppressive CD8+ T cells in the gut-associated lymphoid tissues. PLoS One 5(10):e15373
97. Cai J, Lee J, Jankowska-Gan E, Derks R, Pool J, Mutis T, Goulmy E, Burlingham WJ (2004) Minor H antigen HA-1-specific regulator and effector CD8+ T cells, and HA-1 microchimerism, in allograft tolerance. J Exp Med 199(7):1017-1023 (Pubitemid 38481093)
98. Wei S, Kryczek I, Zou L, Daniel B, Cheng P, Mottram P, Curiel T, Lange A, Zou W (2005) Plasmacytoid dendritic cells induce CD8+ regulatory T cells in human ovarian carcinoma. Cancer Res 65(12):5020-5026 (Pubitemid 40827308)
99. Gilliet M, Liu YJ (2002) Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells. J Exp Med 195(6):695-704 (Pubitemid 34259715)
100. Huleatt JW, Lefrancois L (1995) Antigen-driven induction of CD11c on intestinal intraepithelial lymphocytes and CD8+ T cells in vivo. J Immunol 154(11):5684-5693
101. Kim SK, Schluns KS, Lefrancois L (1999) Induction and visualization of mucosal memory CD8 T cells following systemic virus infection. J Immunol 163(8):4125-4132 (Pubitemid 29474474)
102. Lin Y, Roberts TJ, Sriram V, Cho S, Brutkiewicz RR (2003) Myeloid marker expression on antiviral CD8+ T cells following an acute virus infection. Eur J Immunol 33(10):2736-2743 (Pubitemid 37337139)
103. Vinay DS, Kim CH, Choi BK, Kwon BS (2009) Origins and functional basis of regulatory CD11c+CD8+ T cells. Eur J Immunol 39(6):1552-1563
104. Beyer M, Wang H, Peters N, Doths S, Koerner-Rettberg C, Openshaw PJ, Schwarze J (2005) The beta2 integrin CD11c distinguishes a subset of cytotoxic pulmonary T cells with potent antiviral effects in vitro and in vivo. Respir Res 6:70
105. Kim YH, Seo SK, Choi BK, Kang WJ, Kim CH, Lee SK, Kwon BS (2005) 4-1BB costimulation enhances HSV-1-specific CD8 + T cell responses by the induction of CD11c+CD8+ T cells. Cell Immunol 238(2):76-86
106. Amrani A, Verdaguer J, Serra P, Tafuro S, Tan R, Santamaria P (2000) Progression of autoimmune diabetes driven by avidity maturation of a T-cell population. Nature 406(6797):739-742
107. Han B, Serra P, Yamanouchi J, Amrani A, Elliott JF, Dickie P, Dilorenzo TP, Santamaria P (2005) Developmental control of CD8 T cell-avidity maturation in autoimmune diabetes. J Clin Invest 115(7):1879-1887 (Pubitemid 40979727)
108. Chen ML, Yan BS, Kozoriz D, Weiner HL (2009) Novel CD8+ Treg suppress EAE by TGF-beta-and IFN-gamma-dependent mechanisms. Eur J Immunol 39(12):3423-3435
109. Singh RP, La Cava A, Wong M, Ebling F, Hahn BH (2007) CD8+ T cell-mediated suppression of autoimmunity in a murine lupus model of peptide-induced immune tolerance depends on Foxp3 expression. J Immunol 178(12):7649-7657 (Pubitemid 46898035)
110. Singh RP, La Cava A, Hahn BH (2008) pConsensus peptide induces tolerogenic CD8+ T cells in lupus-prone (NZB × NZW) F1 mice by differentially regulating Foxp3 and PD1 molecules. J Immunol 180(4):2069-2080
111. York NR, Mendoza JP, Ortega SB, Benagh A, Tyler AF, Firan M, Karandikar NJ (2010) Immune regulatory CNS-reactive CD8+ T cells in experimental autoimmune encephalomyelitis. J Autoimmun 35(1):33-44
112. Kleinewietfeld M, Puentes F, Borsellino G, Battistini L, Rotzschke O, Falk K (2005) CCR6 expression defines regulatory effector/memory-like cells within the CD25(+) CD4+ T-cell subset. Blood 105 (7):2877-2886 (Pubitemid 40446282)
113. Zhou Q, Yan J, Putheti P, Wu Y, Sun X, Toxavidis V, Tigges J, Kassam N, Enjyoji K, Robson SC, Strom TB, Gao W (2009) Isolated CD39 expression on CD4+ T cells denotes both regulatory and memory populations. Am J Transplant 9(10):2303-2311
114. Liu T, Soong L, Liu G, Konig R, Chopra AK (2009) CD44 expression positively correlates with Foxp3 expression and suppressive function of CD4+ Treg cells. Biol Direct 4:40
115. Suzuki H, Shi Z, Okuno Y, Isobe K (2008) Are CD8+CD122+ cells regulatory T cells or memory T cells? Hum Immunol 69(11):751-754
116. Colovai AI, Mirza M, Vlad G, Wang S, Ho E, Cortesini R, Suciu-Foca N (2003) Regulatory CD8+CD28-T cells in heart transplant recipients. Hum Immunol 64(1):31-37 (Pubitemid 36109810)
117. Huang YH, Zozulya AL, Weidenfeller C, Schwab N, Wiendl H (2009) T cell suppression by naturally occurring HLA-G-expressing regulatory CD4+ T cells is IL-10-dependent and reversible. J Leukoc Biol 86(2):273-281
118. Liao F, Rabin RL, Smith CS, Sharma G, Nutman TB, Farber JM (1999) CC-chemokine receptor 6 is expressed on diverse memory subsets of T cells and determines responsiveness to macrophage inflammatory protein 3 alpha. J Immunol 162(1):186-194 (Pubitemid 29018919)
119. Rivino L, Gruarin P, Haringer B, Steinfelder S, Lozza L, Steckel B, Weick A, Sugliano E, Jarrossay D, Kuhl AA, Loddenkemper C, Abrignani S, Sallusto F, Lanzavecchia A, Geginat J (2010) CCR6 is expressed on an IL-10-producing, autoreactive memory T cell population with context-dependent regulatory function. J Exp Med 207(3):565-577
120. Huehn J, Siegmund K, Lehmann JC, Siewert C, Haubold U, Feuerer M, Debes GF, Lauber J, Frey O, Przybylski GK, Niesner U, de la Rosa M, Schmidt CA, Brauer R, Buer J, Scheffold A, Hamann A (2004) Developmental stage, phenotype, and migration distinguish naive-and effector/memory-like CD4+ regulatory T cells. J Exp Med 199(3):303-313 (Pubitemid 38252043)
121. Fletcher JM, Lonergan R, Costelloe L, Kinsella K, Moran B, O'Farrelly C, Tubridy N, Mills KH (2009) CD39+Foxp3+ regulatory T Cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis. J Immunol 183(11):7602-7610
122. Vukmanovic-Stejic M, Zhang Y, Cook JE, Fletcher JM, McQuaid A, Masters JE, Rustin MH, Taams LS, Beverley PC, Macallan DC, Akbar AN (2006) Human CD4+CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo. J Clin Invest 116(9):2423-2433 (Pubitemid 44330141)
123. Godebu E, Summers-Torres D, Lin MM, Baaten BJ, Bradley LM (2008) Polyclonal adaptive regulatory CD4 cells that can reverse type I diabetes become oligoclonal long-term protective memory cells. J Immunol 181(3):1798-1805
124. Chang CC, Vlad G, D'Agati VD, Liu Z, Zhang QY, Witkowski P, Torkamani AA, Stokes MB, Ho EK, Cortesini R, Suciu-Foca N (2010) BCL6 is required for differentiation of Ig-like transcript 3-Fc-induced CD8 + T suppressor cells. J Immunol 185(10):5714-5722
125. Vlad G, King J, Chang CC, Liu Z, Friedman RA, Torkamani AA, Suciu-Foca N (2011) Gene profile analysis of CD8(+) ILT3-Fc induced T suppressor cells. Hum Immunol 72 (2):107-114
126. de Kleer IM, Wedderburn LR, Taams LS, Patel A, Varsani H, Klein M, de Jager W, Pugayung G, Giannoni F, Rijkers G, Albani S, Kuis W, Prakken B (2004) CD4+CD25 bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis. J Immunol 172(10):6435-6443 (Pubitemid 38621253)
127. Korn T, Reddy J, Gao W, Bettelli E, Awasthi A, Petersen TR, Backstrom BT, Sobel RA, Wucherpfennig KW, Strom TB, Oukka M, Kuchroo VK (2007) Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat Med 13(4):423-431 (Pubitemid 46559831)
128. Baek HJ, Zhang L, Jarvis LB, Gaston JS (2008) Increased IL-4 + CD8+ T cells in peripheral blood and autoreactive CD8+ T cell lines of patients with inflammatory arthritis. Rheumatology (Oxford) 47(6):795-803 (Pubitemid 351796363)
129. Kao JK, Hsue YT, Lin CY (2007) Role of new population of peripheral CD11c (+) CD8(+) T cells and CD4 (+) CD25 (+) regulatory T cells during acute and remission stages in rheumatoid arthritis patients. J Microbiol Immunol Infect 40 (5):419-427
130. Chatenoud L, Primo J, Bach JF (1997) CD3 antibody-induced dominant self tolerance in overtly diabetic NOD mice. J Immunol 158(6):2947-2954 (Pubitemid 127470558)
131. Cernea S, Herold KC (2010) Monitoring of antigen-specific CD8 T cells in patients with type 1 diabetes treated with antiCD3 monoclonal antibodies. Clin Immunol 134(2):121-129
132. Billerbeck E, Thimme R (2008) CD8+ regulatory T cells in persistent human viral infections. Hum Immunol 69(11):771-775
133. Joosten SA, Ottenhoff TH (2008) Human CD4 and CD8 regulatory T cells in infectious diseases and vaccination. Hum Immunol 69(11):760-770
134. Couper KN, Blount DG, Riley EM (2008) IL-10: the master regulator of immunity to infection. J Immunol 180(9):5771-5777
135. Rouse BT, Sarangi PP, Suvas S (2006) Regulatory T cells in virus infections. Immunol Rev 212:272-286 (Pubitemid 44116714)