Cytoadherence of lymphocytes from type I diabetic subjects to insulin-secreting cells. Marker of anti-beta-cell cellular immunity

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Abstract
We studied the ability of lymphocytes from type I (insulin-dependent) diabetic patients to adhere to murine β-cells. Lymphocytes from 17 recent-onset type I diabetic subjects (1 yr) who taken as a group presented a normal number of RIN rosetting lymphocytes. The islet specificity of these diabetic rosettes was confirmed because, compared with controls, lymphocytes from recent-onset type I diabetic subjects also displayed a greater intensity of adherence to normal mouse islets but not to unrelated K562 and TS cell lines. As demonstrated by indirect immunofluorescence studies, these diabetic rosettes contained 54% of T-lymphocytes (OKT3+, OKT4+, or OKT8+), whereas only 20% of T-lymphocytes were found in background rosettes. The high percentage (66%) of la+ cells found in diabetic rosettes suggests that at least some of the cytoadherent T-lymphocytes from recent-onset type I diabetic subjects are activated. Natural killer (NK) cells do not seem to be the major cell type implicated in this phenomenon, because Leu 11+ cells were less represented in diabetic rosettes (25%) than in background rosettes (53%). Moreover, the NK lytic activity of lymphocytes from 12 recent-onset type I diabetic subjects was lower than that of 12 control subjects (21.6 ± 2.8 vs. 31.2 ± 3.3, P < .02) and even inversely correlated to the number of rosetting lymphocytes ( r = −.8, P < .005). These diabetic rosettes thus seem to represent a new marker of anti-β-cell cellular immunity in recent-onset type I diabetic subjects, more likely involving activated T-lymphocytes than NK cells.