Abstract
Cloned T cell lines expressing either CD4 or CD8 have been isolated from the islets of acutely diabetic NOD mice. These cloned T cell lines respond by proliferating specifically to islets from mice bearing MHC gene products of the NOD strain. Adoptive transfer of cloned T cell lines into irradiated recipients shows intense insulitis and occasional frank diabetes in recipients of both CD4+ and CD8+ cloned T cell lines, but only mild insulitis and no overt disease in recipients of either CD4 or CD8 cloned T cell lines alone. This experimental system will be used to probe three areas of insulin-dependent diabetes mellitus: first, what is the pathogenesis of ß cell destruction in IDDM. Second, what it the exact nature of the ligand recognized on ß cells by CD4+ and CD8+ cloned T cells. Third, what is the nature of the autoreactive T cell receptor, and are T cells mediating islet destruction in NOD mice homogeneous, oligoclonal, or highly variable in the expression of cell surface T cell receptors.
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References
Bendelac AC, Carnaud C, Boitard C, Bach JF (1987) Syngeneic transfer of autoimmune diabetes from diabetic NOD mice to healthy neonates. Requirement for both L3T4+ Lyt-2+ T cells. J exp Med 166: 823–832
Hanahan D (1985) Heritable formation of pancreatic ß cell tumors in transgeic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature 315: 115–122
Hayward AR, Cobbald SP, Waldmann H, Cooke A, Simpson E (1988) Delay in onset of insulitis in NOD mice following a single injection of CD4 and CD8 antibodies. J Autoimmunity 1: 191–96
Janeway CA Jr, Yagi J, Conrad PJ, Katz, ME, Jones B, Vroegop S, Buxser S (1989) T cell responses to Mls and to bacterial proteins that mimic its behavior. Immunol Rev 107: 61–88, 1989.
Miller BJ, Appel MC, O’Neil JJ, Wicker LS (1988) Both the Lyt-2+ and L3T4+ T cell subsets are required for the transfer of diabetes in nonobese diabatic mice. J Immunol 140: 52–58
Nishimoto H, Kikutani H, Yamamura K, Kishimoto T (1987) Prevention of autoimmune insulitis by expression of I-E molecules in NOD mice. Nature 328: 432–434
Shizuru JA, Taylor-Edwards C, Banks BA, Gregory AK, Fathman CG (1988) Immunotherapy of the nonobese diabetic mouse: treatment with an antibody to T-helper lymphocytes. Science 240: 659–62
Sutherland DER, Silbey R, Xu XZ, Michael A, Srikanta S, Taub F, Najarian J, Goetz FC (1984) Twin-to-twin pancreas transplantation: reversal and reenactment of the pathogenesis of type I diabetes. Trans Assoc Am Physicians 97: 80–87
Swain SL (1983) T cell subsets and the recognition of MHC class. Immunol Rev 74: 129–142
Todd JA, Acha-Orbea H, Bell JI, Chao N, Fronek Z, Jacob CO, McDermott M, Sinha AA, Timmerman L, Steinman L, McDevitt, HO (1988) A molecular basis for MHC class II-associated autoimmunity. Science 240: 1003–1009
Todd JA, Bell JI, McDevitt HO (1987) HLA-DQß gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 329: 559–604
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© 1990 Springer-Verlag Berlin Heidelberg
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Reich, EP., Rath, S., Sherwin, R., McDevitt, H., Janeway, C.A. (1990). Autoreactive Cloned T Cell Lines in Murine Insulin-Dependent Diabetes Mellitus. In: Demaine, A.G., Banga, JP., McGregor, A.M. (eds) The Molecular Biology of Autoimmune Disease. NATO ASI Series, vol 38. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75133-2_21
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DOI: https://doi.org/10.1007/978-3-642-75133-2_21
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