MECHANISMS OF CELLULAR IMMUNE RESPONSES

我们的研究继续强调表征细胞表面分子 促进T细胞功能，以及定义它们的调节 T细胞分化。今年取得了重大进展， T细胞粘附于内皮的关键区域。 我们的工作加强了 结合通过至少3个步骤的级联发生的模型：系链， 触发器，附着力强。T细胞的触发步骤是 最不明确的。我们已经发现了两种“促粘附”细胞因子， 有望成为生理触发因子：MIP-1 β和HGF。MIP-1 β：l） 诱导T细胞粘附至内皮配体VCAM-1; 2）可以 保留在蛋白聚糖上以介导其粘附诱导; 3）在 扁桃体和淋巴结中的内皮表面;和4）是趋化性的 对于T细胞。肝细胞生长因子（HGF）在结构上 与MIP-1 β完全不同，以前没有免疫学 相关性，我们发现它在功能上是相似的：对T 细胞以及诱导T细胞粘附。免疫组织学研究 鉴定炎症肝脏等部位内皮细胞上的HGF。我们提出 这些因子通过结合到 蛋白聚糖我们已经开发了一个更广泛的生理模型，这种亲- 粘附性细胞因子通过一种专门的 成纤维细胞网状管道系统。 在整合素的研究中， 介导对内皮的强粘附。流式细胞术和2D凝胶分析 主要鉴定α 6 β 1、α 4 β 1、α 4 β 7和 α 5 β 1对T细胞的影响。整合素的低均匀表达见于 幼稚细胞和记忆细胞上更高的选择性表达， 包括一个新定义的CD 4细胞亚群， 阿尔法4。最后，我们组织了即将举行的第五届 白细胞分化抗原国际研讨会， 确定几乎所有已知白细胞表面的表达水平 许多谱系细胞上的分子。

Our studies continue to emphasize characterizing cell surface molecules which facilitate T cell function, as well as defining their regulation with T cell differentiation. Major advances have been made this year in the critical area of T cell adhesion to endothelium. Our work strengthens the model that binding occurs via a cascade of at least 3 steps: tether, trigger, strong adhesion. The triggering step for T cells has been the least well defined. We have discovered two "pro-adhesive" cytokines which promise to be physiologic triggers: MIP-1beta and HGF. MIP-1beta: l) induces T cell adhesion to the endothelial ligand VCAM-1; 2) can be retained on proteoglycan to mediate its adhesion-induction; 3) is found at the endothelial surface in tonsil and lymph node; and 4) is chemotactic for T cells. Although, hepatocyte growth factor (HGF) is structurally completely different from MIP-1beta and previously had no immunologic relevance, we find it is functionally similar: strongly chemotactic for T cells as well as inducing T cell adhesion. Immunohistologic studies identify HGF on endothelium at sites such as inflamed liver. We propose that these factors are retained at the endothelial surface by binding to proteoglycan. We have developed a broader physiologic model that such pro- adhesive cytokines are delivered to endothelium by a specialized fibroblastic reticular conduit system. In studies of the integrins which mediate strong adhesion to endothelium. Flow cytometry and 2D-gel analysis identifies predominantly alpha6beta1, alpha4beta1, alpha4beta7, and alpha5beta1 on T cells. Low uniform expression of integrins is seen on naive cells and higher more selective expression on memory cells, including a newly defined subset of CD4 cells virtually negative for alpha4. Finally, we have organized a major component of the upcoming Fifth International Workshop on Leukocyte Differentiation Antigen which will determine the level of expression of virtually all known leukocyte surface molecules on cells of many lineages.