Multiparameter immunologic studies in patients with newly diagnosed type 1 insulin-dependent diabetes mellitus

Peripheral blood mononuclear cells from patients with Type 1 diabetes mellitus were examined for the proportion of monoclonal antibody-defined T-cell subsets, natural killer (NK) cells, and macrophages and the proliferative response to phytohemagglutinin (PHA), Concanavalin A (Con A), pokeweed mitogen (PWM) and in the autologous mixed lymphocyte reaction (AMLR) and allogeneic mixed lymphocyte reaction (MLR). The in vitro response of purified IL-2 on PHA- and PWM-induced proliferative response was also examined. Total T cells (Leu 1+), helper/inducer phenotype (Leu 3+) T cells, suppressor/cytotoxic phenotype (Leu 2+) T cells, surface Ig+ B lymphocytes and monoclonal antibody-defined monocytes (Mac +) in patient group were comparable to the control group. The Leu 7+ NK cells were, however significantly (p less than 0.05) decreased in the diabetic group. The NK function was also deficient in the diabetic group when compared to healthy non-diabetic controls. The proliferative responses to all 3 concentrations of PHA, PWM, and Con A, and in the MLR were similar in 2 groups. However, the proliferative response in the AMLR was significantly reduced (p less than 0.05) in the diabetic group. Exogenous purified IL-2 failed to induce any enhancement in the PHA- and PWM-induced proliferative response; this was in contrast to control group in which IL-2 enhanced proliferative response to both mitogens. This study demonstrates deficiency of the AMLR, Leu 7+ and of natural killer cell function and unresponsiveness of mitogen-activated T cells to purified IL-2. The significance of these findings is discussed.