Activated T lymphocytes from patients with high risk of type I diabetes mellitus have different ability to produce interferon-gamma, interleukin-6 and interleukin-10 and undergo anti-CD95 induced apoptosis after insulin stimulation

Type I Diabetes mellitus (DM1) is the effect of T cell dependent autoimmune destruction of insulin producing beta cells in the pancreas islet. T cells are activated in response to islet dominant autoantigens, the result being the development of DM1. Insulin is one of the islet autoantigens responsib le for activation of T lymphocyte functions, inflammatory cytokine producti on and development of DM1. The experiments reported in this study have show n the spontaneous increase of CD95 molecule expression on lymphocytes of th e first-degree relatives of DM1 patients. The autoantigen insulin is respon sible for stimulation in vitro of potentially hazardous 'memory' lymphocyte s to produce interleukin-6 (IL-6) and interleukin-10 (IL-10) interleukins. Insulin induced stimulation of lymphocytes in vitro was observed in patient s at high risk of developing diabetes mellitus (prediabetics). Phytohaemagg lutinin (PHA) stimulates lymphocytes of all groups in the same way. Stimula ted lymphocytes in second cultures undergo apoptosis induced with anti-Fas specific antibodies. The deletion in vitro of resting peripheral lymphocyte s is nonfunctional. Insulin activated T lymphocytes, which undergo apoptosi s were not observed in peripheral blood of healthy people and in patients w ith DM1. This observation suggests that insulin is involved as autoantigen in DM1 progression in patients with high risk of diabetes type I. The autor eactive T lymphocytes may persist in peripheral blood of patients with high risk DM1. Defective elimination of autoreactive T cells may result in auto destructive damage of islets beta cells in the prediabetic stage and diseas e progression to DM1. (C) 2001 Elsevier Science B.V. All rights reserved.