Studies on molecular mechanisms of autoimmune diseases

自身免疫耐受的分子机制和自身免疫性疾病的发病机制是免疫学研究的中心问题之一。为了解决以下问题，美日两国免疫学家进行了合作研究：1.T细胞正负选择的分子机制；2.自身耐受和自身免疫性疾病中的抗原肽；3.细胞因子及其受体与自身免疫性疾病的关系；4.转基因和敲除小鼠在免疫调节研究中的作用；5.MHC与自源肽的相互作用及其T细胞识别；6.多基因家族的表达调控与自身免疫性疾病。T.Honjo博士大部分时间都在与美国国立卫生研究院的著名免疫学家讨论他关于B淋巴细胞耐受和自身免疫性疾病治疗的最新结果，如W.Paul博士，M.Leonald博士，J.Ashw…博士作者声明：More Well，R.Schwartz and P.MezingerHonjo发现，在新西兰黑鼠的腹膜腔内反复注射H2O降低了自身免疫性疾病的发生频率。提示CD5~+B细胞可能参与了自身免疫性疾病的发病过程。在这样的讨论中，他与遗传学系的科学家合作，同意于1994年8月在美国国立卫生研究院举办程序性细胞死亡国际会议。T.Sasazuki博士拜访了哈佛大学(Boston University)的Jack Strominger、Don Willey和Chikao Morimoto教授，纽约斯隆·凯特林癌症研究所的Bo Dupont教授和Hugh O.McDevitt教授，Mark Davis和Garry Fathman在斯坦福大学(Staford)讨论和交流了新的信息和试剂，以促成以下合作工作：1.基于HLA-DR1结晶学的HLA-DR分子和抗原肽的相互作用(J.Strominger，D.Willey)；2.通过黏附分子的相互作用进行免疫调节(C.Morimoto)；3.通过HLA II类分子的信号转导(B.Dupont)4.MHC II类分子在调节T细胞库中的作用(H.O.McDevitt，H.O.McDevitt，M.Davis，G.Fathman)。较少

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