Distinct local immunogenic stimuli dictate differential requirements for CD4⁺ and CD8⁺ T cell subsets in the pathogenesis of spontaneous autoimmune diabetes

References

• Atkinson MA, Eisenbarth GS. Type 1 diabetes: New perspectives on disease pathogenesis and treatment. Lancet 2001; 358: 221–229
   PubMed Web of Science ®Google Scholar
• Wicker LS, Clark J, Fraser HI, Garner VES, Gonzalez-Munoz A, Healy B, Howlett S, Hunter K, Rainbow D, Rosa RL. Type 1 diabetes genes and pathways shared by humans and NOD mice. J Autoimmun 2005; 25: 29–33
   PubMed Web of Science ®Google Scholar
• Jones EY, Fugger L, Strominger JL, Siebold C. MHC class II proteins and disease: A structural perspective. Nat Rev Immunol 2006; 6: 271–282
   PubMed Web of Science ®Google Scholar
• Maier LM, Wicker LS. Genetic susceptibility to type 1 diabetes. Curr Opin Immunol Autoimmun Allergy Hypersensitivity 2005; 17: 601–608
   PubMed Web of Science ®Google Scholar
• Wen L, Wong FS, Sherwin R, Mora C. Human DQ8 can substitute for murine I-Ag7 in the selection of diabetogenic T cells restricted to I-Ag7. J Immunol 2002; 168: 3635–3640
   PubMed Web of Science ®Google Scholar
• Yu B, Gauthier L, Hausmann DH, Wucherpfennig KW. Binding of conserved islet peptides by human and murine MHC class II molecules associated with susceptibility to type 1 diabetes. Eur J Immunol 2000; 30: 2497–2506
   PubMed Web of Science ®Google Scholar
• Suri A, Walters JJ, Gross ML, Unanue ER. Natural peptides selected by diabetogenic DQ8 and murine I-Ag7 molecules show common sequence specificity. J Clin Invest 2005; 115: 2268–2276
   PubMed Web of Science ®Google Scholar
• Liblau RS, Singer SM, McDevitt HO. Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. Immunol Today 1995; 16: 34–38
   PubMedGoogle Scholar
• Mora C, Wong FS, Chang CH, Flavell RA. Pancreatic infiltration but not diabetes occurs in the relative absence of MHC class II-restricted CD4 T cells: Studies using NOD/CIITA- deficient mice. J Immunol 1999; 162: 4576–4588
   PubMed Web of Science ®Google Scholar
• Wong FS, Visintin I, Wen L, Granata J, Flavell R, Janeway CA. The role of lymphocyte subsets in accelerated diabetes in nonobese diabetic-rat insulin promoter-B7-1 (NOD-RIP-B7-1) mice. J Exp Med 1998; 187: 1985–1993
   PubMed Web of Science ®Google Scholar
• Katz J, Benoist C, Mathis D. Major histocompatibility complex class I molecules are required for the development of insulitis in non-obese diabetic mice. Eur J Immunol 1993; 23: 3358–3360
   PubMed Web of Science ®Google Scholar
• Wicker LS, Leiter EH, Todd JA, Renjilian RJ, Peterson E, Fischer PA, Podolin PL, Zijlstra M, Jaenisch R, Peterson LB. Beta 2-microglobulin-deficient NOD mice do not develop insulitis or diabetes. Diabetes 1994; 43: 500–504
   PubMed Web of Science ®Google Scholar
• McInerney M, Rath S, Janeway C. Exclusive expression of MHC class II proteins on CD45+ cells in pancreatic islets of NOD mice. Diabetes 1991; 40: 648–651
   PubMed Web of Science ®Google Scholar
• Chervonsky AV, Wang Y, Wong FS, Visintin I, Flavell RA, Janeway CA, Jr, Matis LA. The role of Fas in autoimmune diabetes. Cell 1997; 89: 17–24
   PubMed Web of Science ®Google Scholar
• Hamilton-Williams EE, Palmer SE, Charlton B, Slattery RM. Beta cell MHC class I is a late requirement for diabetes. PNAS 2003; 100: 6688–6693
   PubMed Web of Science ®Google Scholar
• Apostolou I, Hao Z, Rajewsky K, von Boehmer H. Effective destruction of Fas-deficient insulin-producing {beta} cells in type 1 diabetes. J Exp Med 2003; 198: 1103–1106
   PubMed Web of Science ®Google Scholar
• Amrani A, Verdaguer J, Anderson B, Utsugi T, Bou S, Santamaria P. Perforin-independent β cell destruction by diabetogenic CD8+ T lymphocytes in transgenic nonobese diabetic mice. J Clin Invest 1999; 103: 1201–1209
   PubMed Web of Science ®Google Scholar
• Kagi D, Odermatt B, Seiler P, Zinkernagel RM, Mak TW, Hengartner H. Reduced incidence and delayed onset of diabetes in perforin-deficient nonobese diabetic mice. J Exp Med 1997; 186: 989–997
   PubMed Web of Science ®Google Scholar
• Wong FS, Janeway CA, Jr. The role of CD4 and CD8 T cells in type 1 diabetes in the NOD mouse. Res Immunol 1997; 148: 327–332
   PubMedGoogle Scholar
• Kent SC, Chen Y, Bregoli L, Clemmings SM, Kenyon NS, Ricordi C, Hering BJ, Hafler DA. Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope. Nature 2005; 435: 224–228
   PubMed Web of Science ®Google Scholar
• Unger WW, Pinkse GG, Mulder-van der Kracht S, van der Slik AR, Kester M, Ossendorp F, Drijfhout JW, Serreze D, Roep BO. Human clonal CD8 autoreactivity to an IGRP islet epitope shared between mice and men. Ann NY Acad Sci 2007; 1103: 192–195
   PubMed Web of Science ®Google Scholar
• Mallone R, Martinuzzi E, Blancou P, Novelli G, Afonso G, Dolz M, Bruno G, Chaillous L, Chatenoud L, Bach J-M, van Endert P. CD8+ T cell responses identify {beta} cell autoimmunity in human type 1 diabetes. Diabetes 2007; 56: 613–621
   PubMed Web of Science ®Google Scholar
• Havari E, Lennon-Dumenil AM, Klein L, Neely D, Taylor JA, McInerney MF, Wucherpfennig KW, Lipes MA. Expression of the B7.1 costimulatory molecule on pancreatic {beta} cells abrogates the requirement for CD4 T cells in the development of type 1 diabetes. J Immunol 2004; 173: 787–796
   PubMed Web of Science ®Google Scholar
• Rajagopalan G, Kudva YC, Chen L, Wen L, David CS. Autoimmune diabetes in HLA-DR3/DQ8 transgenic mice expressing the co-stimulatory molecule B7-1 in the {beta} cells of islets of Langerhans. Int Immunol 2003; 15: 1035–1044
   PubMed Web of Science ®Google Scholar
• Rajagopalan G, Kudva YC, Flavell R, David C. Accelerated diabetes in rat insulin promoter-tumor necrosis factor-α transgenic nonobese diabetic mice lacking major histocompatibility class II molecules. Diabetes 2003; 52: 342–347
   PubMed Web of Science ®Google Scholar
• Wen L, Chen NY, Tang J, Sherwin R, Wong FS. The regulatory role of DR4 in a spontaneous diabetes DQ8 transgenic model. J Clin Invest 2001; 107: 871–880
   PubMed Web of Science ®Google Scholar
• Wen L, Wong FS, Tang J, Chen NY, Altieri M, David C, Flavell R, Sherwin R. In vivo evidence for the contribution of human histocompatibility leukocyte antigen (HLA)-DQ molecules to the development of diabetes. J Exp Med 2000; 191: 97–104
   PubMed Web of Science ®Google Scholar
• Kudva YC, Rajagopalan G, Raju R, Abraham RS, Smart M, Hanson J, David CS. Modulation of insulitis and type 1 diabetes by transgenic HLA-DR3 and DQ8 in NOD mice lacking endogenous MHC class II. Hum Immunol 2002; 63: 987–999
   PubMed Web of Science ®Google Scholar
• Wicker LS, Todd JA, Peterson LB. Genetic control of autoimmune diabetes in the NOD mouse. Annu Rev Immunol 1995; 13: 179–200
   PubMed Web of Science ®Google Scholar
• Anderson MS, Bluestone JA. The nod mouse: A model of immune dysregulation. Annu Rev Immunol 2005; 23: 447–485
   PubMed Web of Science ®Google Scholar
• Christianson S, Shultz L, Leiter E. Adoptive transfer of diabetes into immunodeficient NOD-scid/scid mice. Relative contributions of CD4+ and CD8+ T cells from diabetic versus prediabetic NOD.NON-Thy-1a donors. Diabetes 1993; 42: 44–55
   PubMed Web of Science ®Google Scholar
• Guerder S, Meyerhoff J, Flavell R. The role of the T cell costimulator B7-1 in autoimmunity and the induction and maintenance of tolerance to peripheral antigen. Immunity 1994; 1: 155–166
   PubMed Web of Science ®Google Scholar
• Guerder S, Picarella DE, Linsley PS, Flavell RA. Costimulator B7-1 confers antigen-presenting-cell function to parenchymal tissue and in conjunction with tumor necrosis factor alpha leads to autoimmunity in transgenic mice. Proc Natl Acad Sci USA 1994; 91: 5138–5142
   PubMed Web of Science ®Google Scholar
• Harlan DM, Barnett MA, Abe R, Pechhold K, Patterson NB, Gray GS, June CH. Very-low-dose streptozotocin induces diabetes in insulin promoter-mB7-1 transgenic mice. Diabetes 1995; 44: 816–823
   PubMed Web of Science ®Google Scholar
• McInerney MF, Rath S, Janeway CA, Jr. Exclusive expression of MHC class II proteins on CD45+ cells in pancreatic islets of NOD mice. Diabetes 1991; 40: 648–651
   PubMed Web of Science ®Google Scholar
• Suri A, Katz JD. Dissecting the role of CD4+ T cells in autoimmune diabetes through the use of TCR transgenic mice. Immunol Rev 1999; 169: 55–65
   PubMed Web of Science ®Google Scholar
• Eggena MP, Walker LSK, Nagabhushanam V, Barron L, Chodos A, Abbas AK. Cooperative roles of CTLA-4 and regulatory T cells in tolerance to an islet cell antigen. J Exp Med 2004; 199: 1725–1730
   PubMed Web of Science ®Google Scholar
• Mandrup-Poulsen T, Helqvist S, Molvig J, Wogensen LD, Nerup J. Cytokines as immune effector molecules in autoimmune endocrine diseases with special reference to insulin-dependent diabetes mellitus. Autoimmunity 1989; 4: 191–218, discussion 219–234
   PubMedGoogle Scholar
• von Herrath MG, Dockter J, Oldstone MBA. How virus induces a rapid or slow onset insulin-dependent diabetes mellitus in a transgenic model. Immunity 1994; 1: 231–242
   PubMed Web of Science ®Google Scholar
• Castellino F, Germain RN. Cooperation between CD4+ and CD8+ T cells: When, where, and how. Annu Rev Immunol 2006; 24: 519–540
   PubMed Web of Science ®Google Scholar
• Behrens GMN, Li M, Davey GM, Allison J, Flavell RA, Carbone FR, Heath WR. Helper requirements for generation of effector CTL to Islet {beta} cell antigens. J Immunol 2004; 172: 5420–5426
   PubMed Web of Science ®Google Scholar
• Beuneu H, Garcia Z, Bousso P. Cutting edge: Cognate CD4 help promotes recruitment of antigen-specific CD8 T cells around dendritic cells. J Immunol 2006; 177: 1406–1410
   PubMed Web of Science ®Google Scholar
• Bullock TNJ, Yagita H. Induction of CD70 on dendritic cells through CD40 or TLR stimulation contributes to the development of CD8+ T cell responses in the absence of CD4+ T cells. J Immunol 2005; 174: 710–717
   PubMed Web of Science ®Google Scholar
• Belyakov IM, Isakov D, Zhu Q, Dzutsev A, Klinman D, Berzofsky JA. Enhancement of CD8+ T cell immunity in the lung by CpG oligodeoxynucleotides increases protective efficacy of a modified vaccinia ankara vaccine against lethal poxvirus infection even in a CD4-deficient host. J Immunol 2006; 177: 6336–6343
   PubMed Web of Science ®Google Scholar
• Wang B, Norbury CC, Greenwood R, Bennink JR, Yewdell JW, Frelinger JA. Multiple paths for activation of naive CD8+ T cells: CD4-independent help. J Immunol 2001; 167: 1283–1289
   PubMed Web of Science ®Google Scholar
• Lee LF, Xu B, Michie SA, Beilhack GF, Warganich T, Turley S, McDevitt HO. The role of TNF-alpha in the pathogenesis of type 1 diabetes in the nonobese diabetic mouse: Analysis of dendritic cell maturation. Proc Natl Acad Sci USA 2005; 102: 15995–16000
   PubMed Web of Science ®Google Scholar
• Ohashi P, Oehen S, Aichele P, Pircher H, Odermatt B, Herrera P, Higuchi Y, Buerki K, Hengartner H, Zinkernagel R. Induction of diabetes is influenced by the infectious virus and local expression of MHC class I and tumor necrosis factor-alpha. J Immunol 1993; 150: 5185–5194
   PubMed Web of Science ®Google Scholar
• Laufer T, von Herrath M, Grusby M, Oldstone M, Glimcher L. Autoimmune diabetes can be induced in transgenic major histocompatibility complex class II-deficient mice. J Exp Med 1993; 178: 589–596
   PubMed Web of Science ®Google Scholar
• Herrera PL, Harlan DM, Fossati L, Izui S, Huarte J, Orci L, Vassalli JD, Vassalli P. A CD8+ T-lymphocyte-mediated and CD4+ T-lymphocyte-independent autoimmune diabetes of early onset in transgenic mice. Diabetologia 1994; 37: 1277–1279
   PubMed Web of Science ®Google Scholar
• Herrera PL, Harlan DM, Vassalli P. A mouse CD8 T cell-mediated acute autoimmune diabetes independent of the perforin and Fas cytotoxic pathways: Possible role of membrane TNF. PNAS 2000; 97: 279–284
   PubMed Web of Science ®Google Scholar