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的核心问题之一。为了仔细阅读以下问题，综述了美日两国免疫学家的合作研究：1. T细胞正负选择的分子机制; 2.与自身免疫耐受和自身免疫性疾病有关的抗原肽; 3.细胞因子及其受体与自身免疫性疾病的关系; 4.转基因小鼠和基因敲除小鼠在免疫调节研究中的作用; 5. MHC和自身免疫肽及其T细胞识别6. HLA多基因家族表达的调控与自身免疫性疾病这些合作研究的成果如下：T.Honjo博士花了大部分时间与NIH的著名免疫学家如Dr.W.Paul，M.Leonald，J.Ashw等讨论他关于B淋巴细胞耐受和自身免疫性疾病治疗的最新结果 ...更多信息 题名其余部分：R.Schwartz and P. Mezinger. Honjo发现，反复向新西兰黑小鼠腹腔注射H_2O可降低自身免疫性疾病的发生率。结果提示，CD 5 ^+B细胞可能参与了自身免疫性疾病的发病。1994年8月，他与美国国立卫生研究院遗传学系的科学家合作，在美国国立卫生研究院组织了一次关于细胞死亡的国际会议。斯坦福大学医学中心和DNAX，通过相互交换实验材料，K.Okumura博士成功地克隆了编码巨噬细胞和B细胞上T细胞活化方面最重要的粘附分子之一（B70）的未知基因。T.Sasazuki博士拜访了哈佛大学（波士顿）的Jack Strominger，Don Willey和Chikao Morimoto教授，斯隆凯特林癌症研究所的博·杜邦（纽约）与斯坦福大学的Hugh O.McDevitt、Mark Davis和Garry Fathman讨论和交流新的信息以及试剂，以进行“HLA多基因家族产物的调节”的合作实验室工作，具体如下：1. HLA-DR分子与抗原肽的相互作用（J.Strominger，2.通过粘附分子相互作用的免疫调节（C.Morimoto）.3.通过HLA II类分子的信号转导（B.Dupont）4.使用HLA II类和T细胞受体转基因小鼠，MHC II类分子在调节T细胞谱系中的作用（H.O.McDevitt，M.Davis，G.Fathman）.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