We intend to study factors which induce or amplify MHC antigen expression on parenchymal cells of allografts. Pancreatic islet cells should prove interesting for these studies, since passenger leukocytes with antigen presenting function can be deleted from them by tissue culture, and since islet cells ordinarily express only class I antigens, but can be induced by exposure to lymphokines (such as interferon) to express class II antigens and to increase their expression of class I antigens. Assessment of whether modulation of MHC antigens imparts to islets the potential to present alloantigens or nominal antigens may provide insight into intragraft immuno-regulating mechanisms. We will employ in vitro cytotoxicity assays to test the effect of hyperexpression of class I antigens on islet lysis. Islets induced to express class II neo-antigens will be assessed for antigen presenting capability in vitro and in islet transplant experiments. Islets obtained from a new line of transgenic mice in which beta cell class II expression has been induced by recombinant DNA techniques will be of particular interest. Islet transplant studies will attempt to determine whether Ia bearing beta cells can initiate rejection or autoimmunity. If parenchymal cells are themselves found capable of presenting antigen to T lymphocytes, then blocking MHC antigen induction might be a promising mode of therapeutic intervention before or during allograft rejection.
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