Recombinant gamma interferon induces class II major histocompatibility complex antigens on insulinoma cells

Aberrant expression of major histocompatibility (MHC) antigens has been implicated as a factor contributing to organ-specific autoimmunity, such as progressive loss of pancreatic beta cells in type 1 diabetes. We investigated the potential of a rat beta cell tumour, RINM5F, to express enhanced levels of MHC antigens in vitro. To this purpose we treated RINM5F cells in vitro with recombinant rat gamma interferon (rIF gamma). We used monoclonal antibodies to RT1.A (class I) and RT1.B (class II) antigens of the rat MHC in conjunction with flowcytometry and immunoperoxidase techniques to analyse the expression of MHC antigens. Untreated RINM5F cells express low levels of RT1.A, whereas they are negative for RT1.B. Treatment with rIF gamma appeared to increase the expression of RT1.A antigens substantially. Most importantly, RT1.B antigens were newly expressed by rat insulinoma cells in vitro after treatment with rIF gamma. To our knowledge this is the first documentation of the potential of beta cells or their derivatives to express class II MHC antigens following IF gamma-treatment. This mechanism may play an important role in the augmentation and perpetuation of insulitis leading to type 1 diabetes mellitus.