Class II MHC antigen induction on rat insulinoma (RINm5F) and colon carcinoma (TS) cells by co-culture with diabetic and normal xenogenic lymphocytes

Two MHC Class II-negative rat epithelial cell lines (RINm5F beta-cells and TS colic cells) were co-cultured with xenogenic lymphocytes from Type I diabetic patients or from low-dose streptozotocin (SZ) diabetic mice. MHC Class II antigens (Ag) were easily induced on both cell lines in such co-culture conditions, representing an experimental approach to insulitis. Our data indicate that: (1) lymphocytes from diabetic patients or from SZ mice were more efficient than lymphocytes from healthy controls in inducing Class II Ag on RIN cells. Lymphocytes from patients with autoimmune thyroid diseases were also more efficient than control lymphocytes, indicating that the ability to induce Class II may be related to the activation of lymphocytes rather than being diabetes-specific. (2) Rat colon carcinoma cells (TS) were also induced to express high levels of Class II Ag upon co-culture with SZ or control mouse lymphocytes. (3) Class II+ RIN cells were observed after 24 h of co-culture; their number increased after 48 and 72 h. The number of class II+ RIN increased proportionally to the number of lymphocytes in the culture. (4) Induction of Class II Ag was obtained by cell-free supernatants of mouse lymphocytes/RIN co-cultures and was inhibited by cyclosporine A, suggesting that Class II induction in this model is mediated by lymphokines. (5) Depletion experiments indicate that both monocytes and lymphocytes play a role in this Class II induction.