Studies on molecular mechanisms of autoimmune diseases

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Molecular mechanisms of self-tolerance and pathogenesis of autoimmune diseases are one of the central issues in the immunology. In order to peruse the following questions, the collaborative studies between immunologists in the US and Japan have been undertaken.1.Molecular mechanism of positive and negative selection of T cells.2.Antigenic peptides involved in autotolerance and autoimmune diseases.3.Cytokines and their receptors and their relationship with autoimmune diseases.4.Transgenic as well as knock out mice in the studies on the immune regulation.5.Interaction between MHC and autigenic peptides and their recognition by T cells.6.Regulation of the expression of the HLA multi-gene family and autoimmune diseases.The outcome obtained by these collaborative studies are as follows ;Dr.T.Honjo spent most of his time by discussing with his latest results about B lymphocyte tolerance and treatment of autoimmune diseases with prominent immunologists in NIH like Dr.W.Paul, M.Leonald, J.Ashw … More ell, R.Schwartz and P.Mezinger. Honjo found that repeated injection of H_2O into the peritoneal cavity of New Zealand black mice reduced the frequency of autoimmune diseases. The result suggests that CD5^+B cells might be involved in the onset of autoimmune diseases in autoimmune prone New Zealand black mice. During such discussion, he reached agreement to organize International Conference on Programed Cell Death at NIH in August of 1994.By the collaboration with the scientists of Department of Genetics. Stanford Medical Center, and DNAX and by exchanging experimental materials each other, Dr.K.Okumura succeeded to clone the unknown gene coding one of the most important adhesion molecules (B70), in terms of T cell activation on macrophage and B cell.Dr.T.Sasazuki visited professors Jack Strominger, Don Willey, and Chikao Morimoto at Harvard University (Boston), Bo Dupont at Sloan Ketterling Cancer Institute (New York) and Hugh O.McDevitt, Mark Davis and Garry Fathman at Stanford University (Staford) to discuss and exchange the new informations as well as reagents to persue collaboratory work on "Regulation by the products of HLA multigene family" as followings :1.Interaction of HLA-DR molecules and antigenic peptides based on the crystallography of HLA-DR1 (J.Strominger, D.Willey)2.Immune regulation through the interaction of adhesion molecules (C.Morimoto).3.Signal transduction through HLA class II molecules (B.Dupont)4.Role of MHC class II molecules in regulating the T cell repertoire using HLA class II and T cell receptor transgenic mice (H.O.McDevitt, M.Davis, G.Fathman). Less