T-CELL REACTIVITY TO BETA-CELL MEMBRANE-ANTIGENS ASSOCIATED WITH BETA-CELL DESTRUCTION IN IDDM

Insulin-dependent diabetes mellitus (IDDM) results from a T-cell-media ted destruction of the insulin-producing beta-cells. In this study, me designed a sensitive assay to detect and identify islet cell-reactive T-cells in patients with newly diagnosed IDDM. The relation between T -cell recognition of beta-cell antigens with IDDM and the pathogenesis of the disease (the beta-cell destruction process) was tested in a la rge group of IDDM patients and compared with T-cell responses in nondi abetic children with other chronic inflammations and in immunologicall y normal, age-matched control subjects. The results demonstrate that p eripheral blood T-cells reacting with a beta-cell membrane preparation enriched for insulin-secretory granule antigen were detectable in the majority of newly diagnosed IDDM patients (27 of 40 [67%]; mean stimu lation index [SI] 37.0). Such reactivity was reduced postonset in IDDM patients proportionally to the duration of the disease (11 of 30 [37% ]; mean SI 8.7). Nondiabetic age-matched control subjects showed no re sponses or moderate responses to the granule preparation (4 of 48 [8%] ; mean SI 3.4). The magnitude of the T-cell response was significantly greater in newly diagnosed IDDM patients than in IDDM patients tested at least 2 years postonset (P < 0.001), Two children in remission for insulin dependency (so-called honeymoon period) displayed exceptional ly high proliferative responses to insulin-secretory granules (mean SI 86.7), These results imply that T-cell recognition of insulin-secreto ry granule antigens is associated with IDDM and in particular with the immune-mediated process of beta-cell destruction.