Summary
Approximately 50% of BB rats develop insulinopenic hyperglycaemia and ketosis spontaneously in association with insulitis. Amelioration of the syndrome by immunosuppression suggests a cell mediated immune pathogenesis. Analysis of the cell-mediated immune profile of overtly diabetic and normoglycaemic diabetes prone BB rats indicates that they are lymphocytopenic relative to non-diabetes prone BB rats and that the T cell pool is particularly affected. Furthermore, lymphocytes from diabetic and diabetes prone BB rats, while producing normal responses to the T cell mitogen concanavalin A, do not respond when mixed in vitro with major histocompatibility complex incompatible lymphocytes. This anergy is not restored either by enriching the responding cell population for T cells or by adding exogenous T cell growth promoting factor. Thus BB rats have a numerical and regulatory deficit of their T cells which could be related to their propensity for diabetes.
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Nerup J, Lernmark A (1981) Autoimmunity in insulin-dependent diabetes mellitus. Am J Med 70:135–141
Gepts W, LeCompte P (1981) The pancreatic islets in diabetes. Am J Med 70:105–115
Cudworth AG, Bottazzo GF, Doniah D (1981) Genetic and immunological factors in Type I diabetes. In: Irvine J (ed) Immunology of diabetes. Teviot, pp 67–99
McDevitt HO (1980) Regulation of the immune response by the major histocompatibility system. N Engl J Med 303:1514–1517
Nakhooda AF, Like AA, Chappel CI, Wei CN, Marliss EB (1978) The spontaneously diabetic Wistar rat (the BB rat). Studies prior and during development of the overt syndrome. Diabetologia 14:199–207
Like AA, Williams RM, Kislauskie E, Rossini AA (1981) Neonatal thymectomy prevents spontaneous diabetes in the BB/W rat. Clin Res 29: Abstract 542A.
Like AA, Rossini AA, Guberski DL, Appel MC, Williams RM (1979) Spontaneous diabetes mellitus: reversal and prevention in the BB/W rat with antiserum to rat lymphocytes. Science 206:1421–1423
Naji A, Silvers WK, Barker CF (1981) Islet transplantation in spontaneously diabetic rats. Transplant Proc 13:826–828
Naji A, Silvers WK, Plotkin SA, Dafoe D, Barker CF (1979) Successful islet transplantation in spontaneous diabetes. Surgery 86:218–226
Naji A, Silvers WK, Bellgrau D, Anderson AO, Plotkin S, Barker, CF (1981) Prevention of diabetes in rats by bone marrow transplantation. Ann Surg 194:328–338
Bellgrau D, Wilson DB (1978) Immunological studies of T cell receptors. I. Specifically induced resistance to graft versus host disease in rats mediated by host T cells immune to alloreactive parental T cells. J Exp Med 148:103–114
Julius MH, Simpson E, Herzenberg LA (1973) A rapid method for the isolation of functional thymus derived murine lymphocytes. Eur J Immunol 3:645–649
Gronvik KO, Andersson J (1980) The role of T cell growth stimulating factor in T cell triggering. Immunol Rev 51:35–39
Wilson DB, Marshak A, Howard JC (1976) Specific positive and negative selection of rat lymphocytes reactive to strong histocompatibility antigens: Activation with alloantigen in vitro and in vivo. J Immunol 116:1030–1040
Lubaroff DM, Greiner DL, Reynolds CW (1979) Investigation of T lymphocyte subpopulations in the rat using allogeneic markers. Transplant Proc 11:1092–1094
Oi VT, Jones PP, Goding JW, Herzenberg LA (1978) Properties of monoclonal antibodies to mouse Ig allotypes, H-2 and Ia antigens. Curr Top Microbiol Immunol 81:115–119
Rozing J, Vaessen LMB, VanEwijk W, Lameijer LF (1979) Cross reactivity between mouse Ia antigens and rat Ia-like antigens as determined by monoclonal anti-mouse IaAk antibodies. Transplant Proc 11:1574–1578
Kalant N, Seemayer T (1979) Malignant lymphoma in spontaneously diabetic rats. N Eng J Med 200:737
Colle RD, Guttmann RD, Seemayer T (1981) Spontaneous diabetes mellitus syndrome in the rat. I. Association with the major histocompatibility complex. J Exp Med 154:1237–1242
Cantor H, Boyse EA (1975) Functional subclasses of T lymphocytes bearing different Ly antigens. J Exp Med 141:1390–1399
Cantor H, Gershon RK (1979) Immunological circuits: cellular composition. Fed Proc 38:2058–2064
Naji A, Silvers WK, Bellgrau D, Barker CF (1981) Spontaneous diabetes in rats: Destruction of islets is prevented by immunological tolerance. Science 213:1390–1392
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Bellgrau, D., Naji, A., Silvers, W.K. et al. Spontaneous diabetes in BB rats: Evidence for a T cell dependent immune response defect. Diabetologia 23, 359–364 (1982). https://doi.org/10.1007/BF00253745
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DOI: https://doi.org/10.1007/BF00253745