Active CD4⁺ helper T cells directly stimulate CD8⁺ cytotoxic T lymphocyte responses in wild-type and MHC II gene knockout C57BL/6 mice and transgenic RIP-mOVA mice expressing islet β-cell ovalbumin antigen leading to diabetes

References

• Ohashi PS, Oehen S, Buerki K, Pircher H, Ohashi CT, Odermatt B, Malissen B, Zinkernagel RM, Hengartner H. Ablation of “tolerance” and induction of diabetes by virus infection in viral antigen transgenic mice. Cell 1991; 65: 305–317
   PubMed Web of Science ®Google Scholar
• Oldstone MB, Nerenberg M, Southern P, Price J, Lewicki H. Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: Role of anti-self (virus) immune response. Cell 1991; 65: 319–331
   PubMed Web of Science ®Google Scholar
• Kurts C, Sutherland RM, Davey G, Li M, Lew AM, Blanas E, Carbone FR, Miller JF, Heath WR. CD8 T cell ignorance or tolerance to islet antigens depends on antigen dose. Proc Natl Acad Sci USA 1999; 96: 12703–12707
   PubMed Web of Science ®Google Scholar
• Keene JA, Forman J. Helper activity is required for the in vivo generation of cytotoxic T lymphocytes. J Exp Med 1982; 155: 768–782
   PubMed Web of Science ®Google Scholar
• Bennett SR, Carbone FR, Karamalis F, Miller JF, Heath WR. Induction of a CD8+ cytotoxic T lymphocyte response by cross-priming requires cognate CD4+T cell help. J Exp Med 1997; 186: 65–70
   PubMed Web of Science ®Google Scholar
• Schoenberger SP, Toes RE, van der Voort EI, Offringa R, Melief CJ. T-cell help for cytotoxic T lymphocytes is mediated by CD40–CD40L interactions. Nature 1998; 393: 480–483
   PubMed Web of Science ®Google Scholar
• Bevan MJ. Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay. J Exp Med 1976; 143: 1283–1288
   PubMed Web of Science ®Google Scholar
• Huang AY, Golumbek P, Ahmadzadeh M, Jaffee E, Pardoll D, Levitsky H. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 1994; 264: 961–965
   PubMed Web of Science ®Google Scholar
• Guerder S, Matzinger P. A fail-safe mechanism for maintaining self-tolerance. J Exp Med 1992; 176: 553–564
   PubMed Web of Science ®Google Scholar
• Ridge JP, Di Rosa F, Matzinger P. A conditioned dendritic cell can be a temporal bridge between a CD4+T-helper and a T-killer cell. Nature 1998; 393: 474–478
   PubMed Web of Science ®Google Scholar
• Bourgeois C, Rocha B, Tanchot C. A role for CD40 expression on CD8+T cells in the generation of CD8+T cell memory. Science 2002; 297: 2060–2063
   PubMed Web of Science ®Google Scholar
• Lee BO, Hartson L, Randall TD. CD40-deficient, influenza-specific CD8 memory T cells develop and function normally in a CD40-sufficient environment. J Exp Med 2003; 198: 1759–1764
   PubMed Web of Science ®Google Scholar
• He T, Zong S, Wu X, Wei Y, Xiang J. CD4+T cell acquisition of the bystander pMHC I colocalizing in the same immunological synapse comprising pMHC II and costimulatory CD40, CD54, CD80, OX40L, and 41BBL. Biochem Biophys Res Commun 2007; 362: 822–828
   PubMed Web of Science ®Google Scholar
• Xiang J, Huang H, Liu Y. A new dynamic model of CD8+T effector cell responses via CD4+T helper-antigen-presenting cells. J Immunol 2005; 174: 7497–7505
   PubMed Web of Science ®Google Scholar
• Behrens GM, 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
• Zhang W, Chen Z, Li F, Kamencic H, Juurlink B, Gordon JR, Xiang J. Tumour necrosis factor-alpha (TNF-alpha) transgene-expressing dendritic cells (DCs) undergo augmented cellular maturation and induce more robust T-cell activation and anti-tumour immunity than DCs generated in recombinant TNF-alpha. Immunology 2003; 108: 177–188
   Google Scholar
• Porgador A, Yewdell JW, Deng Y, Bennink JR, Germain RN. Localization, quantitation, and in situ detection of specific peptide-MHC class I complexes using a monoclonal antibody. Immunity 1997; 6: 715–726
   PubMed Web of Science ®Google Scholar
• Moore AC, Gallimore A, Draper SJ, Watkins KR, Gilbert SC, Hill AV. Anti-CD25 antibody enhancement of vaccine-induced immunogenicity: Increased durable cellular immunity with reduced immunodominance. J Immunol 2005; 175: 7264–7273
   PubMed Web of Science ®Google Scholar
• Kurts C, Heath WR, Kosaka H, Miller JF, Carbone FR. The peripheral deletion of autoreactive CD8+T cells induced by cross-presentation of self-antigens involves signaling through CD95 (Fas, Apo-1). J Exp Med 1998; 188: 415–420
   PubMedGoogle Scholar
• Steinaa L, Rasmussen PB, Wegener AM, Sonderbye L, Leach DR, Rygaard J, Mouritsen S, Gautam AM. Linked foreign T-cell help activates self-reactive CTL and inhibits tumor growth. J Immunol 2005; 175: 329–334
   PubMed Web of Science ®Google Scholar
• Christianson SW, Shultz LD, Leiter EH. 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
• O'Reilly LA, Hutchings PR, Crocker PR, Simpson E, Lund T, Kioussis D, Takei F, Baird J, Cooke A. Characterization of pancreatic islet cell infiltrates in NOD mice: Effect of cell transfer and transgene expression. Eur J Immunol 1991; 21: 1171–1180
   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 beta-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
• 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 1993; 187: 1985–1993
   Google Scholar
• Wong FS, Janeway CA, Jr. The role of CD4 and CD8 T cells in type I diabetes in the NOD mouse. Res Immunol 1997; 148: 327–332
   PubMedGoogle Scholar
• D'Souza WN, Schluns KS, Masopust D, Lefrancois L. Essential role for IL-2 in the regulation of antiviral extralymphoid CD8 T cell responses. J Immunol 2002; 168: 5566–5572
   PubMed Web of Science ®Google Scholar
• Antony PA, Piccirillo CA, Akpinarli A, Finkelstein SE, Speiss PJ, Surman DR, Palmer DC, Chan CC, Klebanoff CA, Overwijk WW, Rosenberg SA, Restifo NP. CD8+T cell immunity against a tumor/self-antigen is augmented by CD4+T helper cells and hindered by naturally occurring T regulatory cells. J Immunol 2005; 174: 2591–2601
   PubMed Web of Science ®Google Scholar
• Shi M, Hao S, Chan T, Xiang J. CD4(+) T cells stimulate memory CD8(+) T cell expansion via acquired pMHC I complexes and costimulatory molecules, and IL-2 secretion. J Leukoc Biol 2006; 80: 1354–1363
   Google Scholar
• Huang H, Hao S, Li F, Ye Z, Yang J, Xiang J. CD4+ Th1 cells promote CD8+ Tc1 cell survival, memory response, tumor localization and therapy by targeted delivery of interleukin 2 via acquired pMHC I complexes. Immunology 2007; 120: 148–159
   PubMed Web of Science ®Google Scholar
• Zhou J, Tagaya Y, Tolouei-Semnani R, Schlom J, Sabzevari H. Physiological relevance of antigen presentasome (APS), an acquired MHC/costimulatory complex, in the sustained activation of CD4+T cells in the absence of APCs. Blood 2005; 105: 3238–3246
   PubMed Web of Science ®Google Scholar
• Mostbock S, Catalfamo M, Tagaya Y, Schlom J, Sabzevari H. Acquisition of antigen presentasome (APS), an MHC/costimulatory complex, is a checkpoint of memory T-cell homeostasis. Blood 2007; 109: 2488–2495
   Google Scholar
• Bennett SR, Carbone FR, Karamalis F, Flavell RA, Miller JF, Heath WR. Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature 1998; 393: 478–480
   PubMed Web of Science ®Google Scholar
• Lu Z, Yuan L, Zhou X, Sotomayor E, Levitsky HI, Pardoll DM. CD40-independent pathways of T cell help for priming of CD8(+) cytotoxic T lymphocytes. J Exp Med 2000; 191: 541–550
   PubMedGoogle Scholar
• Ozaki ME, Coren BA, Huynh TN, Redondo DJ, Kikutani H, Webb SR. CD4+T cell responses to CD40-deficient APCs: Defects in proliferation and negative selection apply only with B cells as APCs. J Immunol 1999; 163: 5250–5256
   Google Scholar
• Shepherd DM, Kerkvliet NI. Disruption of CD154:CD40 blocks generation of allograft immunity without affecting APC activation. J Immunol 1999; 163: 2470–2477
   Google Scholar
• Cox JH, McMichael AJ, Screaton GR, Xu XN. CTLs target Th cells that acquire bystander MHC class I-peptide complex from APCs. J Immunol 2007; 179: 830–836
   Google Scholar
• Huang JF, Yang Y, Sepulveda H, Shi W, Hwang I, Peterson PA, Jackson MR, Sprent J, Cai Z. TCR-Mediated internalization of peptide-MHC complexes acquired by T cells. Science 1999; 286: 952–954
   PubMedGoogle Scholar
• Hwang I, Huang JF, Kishimoto H, Brunmark A, Peterson PA, Jackson MR, Surh CD, Cai Z, Sprent J. T cells can use either T cell receptor or CD28 receptors to absorb and internalize cell surface molecules derived from antigen-presenting cells. J Exp Med 2000; 191: 1137–1148
   Google Scholar
• McGuirk P, McCann C, Mills KH. Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: A novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis. J Exp Med 2002; 195: 221–231
   PubMed Web of Science ®Google Scholar
• Zhang X, Huang H, Yuan J, Sun D, Hou WS, Gordon J, Xiang J. CD4-8- dendritic cells prime CD4+T regulatory 1 cells to suppress antitumor immunity. J Immunol 2005; 175: 2931–2937
   Google Scholar
• Zhang ZX, Yang L, Young KJ, DuTemple B, Zhang L. Identification of a previously unknown antigen-specific regulatory T cell and its mechanism of suppression. Nat Med 2000; 6: 782–789
   PubMed Web of Science ®Google Scholar
• Tarbell KV, Yamazaki S, Olson K, Toy P, Steinman RM. CD25+ CD4+T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J Exp Med 2004; 199: 1467–1477
   PubMed Web of Science ®Google Scholar