Inducibility of Ia molecules on keratinocytes reflects genetic control on astrocytes in the brain

We have recently observed strain differences in interferon-gamma (IFN-gamma) induction of Ia on astrocytes in rats and mice that are susceptible or resistant to experimental allergic encephalomyelitis (EAE) (Massa et al., 1987). We now found that keratinocytes cultured from rat skin show the same strain differences as astrocytes. Keratinocytes of EAE-susceptible Lewis rats are induced to higher levels of Ia expression compared to relatively resistant Brown-Norway (BN) rats, independent of the dose of IFN-gamma applied. This difference in regulation is specific for class II histocompatibility molecules because no such differences are seen with class I antigen induction by IFN-gamma. That keratinocytes reflect similar strain differences as astrocytes may be explained by a common ectodermal origin of these epithelial-like cells. This observation allows the determination of the genetic predisposition of an autoimmune response in the central nervous system by skin biopsy. This approach may be of importance in studies of immunopathological phenomena of brain tissue in man such as multiple sclerosis.