The major histocompatibility complex (MHC) genes, primarily of the MHC class II region, are linked to increased susceptibility to autoimmune thyroid disease in animals and humans. The quantity of MHC class II antigens that are expressed on the appropriate cell surface, as well as their allotype, are of vital importance to immune function. We have, therefore, compared MHC class II (RTl.D) gene activation in a newly available Wistar rat thyroid (WRT) cell line (a thyroiditissusceptible strain) with a cloned cell (1B-6) derived from the Fisher rat thyroid cell line (FRTL-5) (a thyroiditis-resistant strain) to determine differences in their degree of MHC class II gene activation and antigen expression. There was no detectable constitutive MHC class II antigen or RTl.D α-chain messenger RNA expression in either WRT or 1B-6 cells. Cultures of both cells expressed MHC class II gene induction in response to recombinant rat γ-interferon (γIF). After 72 h of exposure to 25 U/ml γlF, over 80% of WRT cells expressed class II antigen, detected by flow cytometric assessment, as compared to only 15% of 1B-6 cells. This earlier and greater expression of MHC class II antigen was reflected in the RTl.D α-chain mRNA responses with peak levels in WRT cells after only 24 h of exposure to γIF, a period in which 1B-6 cells showed only minor increases in mRNA. To examine whether these differences in class II MHC expression were thyroid-cell specific, primary pulmonary fibroblast lines from Wistar and Fisher rats were developed and a similar, although less marked, variation in susceptibility to γIF was observed. Hence, those rat strains that are resistant to autoimmune thyroid disease exhibit a fundamental difference in their MHC class II gene responsiveness to cytokines, which may contribute to their disease susceptibility profiles.
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