Low-dose immunosuppression may unmask type I diabetes mellitus by specific inactivation of suppressor cells.
Type I diabetes mellitus is strongly genetically linked to the major histocompatibility complex but relatively few potentially susceptible people, who are presumably frequently exposed to appropriate triggering factors (e.g. viral illness, environmental agents), develop overt disease. It is possible that some such individuals show latent disease (e.g. islet cell antibodies and perhaps local pancreatic pathology) that does not progress. On the basis of animal data and some clinical evidence we speculate that latent disease is controlled by suppressor cells. We suggest that physiological immunosuppression (e.g. with glucocorticoids) may selectively inactivate such T suppressor cells. Such immunomodulation may allow further islet cell destruction to occur and repeated episodes could eventually produce diabetes. Such episodes of altered immunoregulation may be due to intercurrent viral illness, stress, or therapy with low doses of immunosuppressive agents.
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000209:etiology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D051381:Rats; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D001323:Autoantibodies; C024211:islet cell antibody