MECHANISMS OF CELLULAR IMMUNE RESPONSES

我们的研究侧重于两个基本方面：1)表征细胞 促进T细胞识别的表面分子；以及2)分析 人类T细胞亚群和功能T细胞亚群的异质性 这些子集的容量。在理解这些问题上取得了进展 T细胞与内皮细胞相互作用的分子基础。两个新的 分子途径正在被阐明。记忆T细胞的一个子集结合 与内皮细胞上的可诱导配体ELAM-1结合；因为这个途径 不需要事先激活T细胞，这可能是最重要的 在记忆T细胞与炎症的内皮细胞的最初附着中 活着。我们已经定义了CD31分子的许多特征 T细胞的子集，使其成为非常有吸引力的候选细胞 调节T细胞与内皮细胞的黏附。CD31不仅在 粘连，但它也通过多次强烈地诱导粘连 在静息T细胞上存在但相对不黏附的整合素 细胞。T细胞通过其他三种分子与内皮细胞的相互作用 途径：VLA-4/VCAM1，LFA-L/ICAM-1和LFA-L/ICAM-2也已被 系统地分析了。不仅是CD3和CD31，还有T细胞 表面分子CD7和CD28可增强细胞的黏附功能 T细胞表达多种整合素。此外，黏附分子 调节T细胞激活，正如我们最近的研究表明的那样 Vla-4/VCAM-1，证实和扩展了LFA-L/ICAM-1的研究 互动。不同品种表型异质性的详细分析 外周血中的CD4+T细胞，以及最近的CD8+T细胞，识别 表面表型调控的显著复杂性，如：1)CD4 存储单元可以根据数量被细分为两个子集 CD45RB亚型表达的差异；2)记忆细胞似乎 在CD8细胞中的含量远低于CD4细胞；3)VLA-4突出 作为CD_4细胞和CD_4细胞间分化的重要参数 在CD8细胞中。简而言之，我们的研究突出并阐明了 黏附、活化与分化的关系。

Our studies emphasize two fundamental areas: 1) characterizing cell surface molecules which facilitate T cell recognition; and 2) analysis of heterogeneity among subsets of human T cells and of the functional capacities of those subsets. Progress has been made in understanding the molecular basis of T cell interactions with endothelium. Two new molecular pathways are being elucidated. A subset of memory T cells bind to the inducible ligand ELAM-1 on endothelial cells; since this pathway does not require prior T cell activation, it may be of primary importance in the initial attachment of memory T cells to inflamed endothelium in vivo. We have defined many characteristics of the molecule CD31 on a subset of T cells which make it a very attractive candidate for regulating T cell adhesion to endothelium. Not only does CD31 mediate adhesion, but it also powerfully induces adhesion by the multiple integrins which are present but relatively nonadhesive on resting T cells. T cell interaction with endothelium via three other molecular pathways: VLA-4/VCAM 1, LFA-l/ICAM-1 and LFA-l/ICAM-2 has also been systematically analyzed. Not only CD3 and CD31, but also the T cell surface molecules CD7 and CD28 can augment the adhesive function of multiple integrins expressed by T cells. Furthermore, adhesion molecules regulate T cell activation, as illustrated by our recent studies with VLA-4/VCAM-1, which confirm and extend ongoing studies of LFA-l/ICAM-1 interactions. Detailed analysis of phenotypic heterogeneity among peripheral blood CD4+ T cells, and more recently CD8+ T cells, identifies marked complexity of regulation of surface phenotype such as: 1) CD4 memory cells can be subdivided into two subsets based on quantitative differences in expression of the CD45RB isoform; 2) Memory cells seem to be much less abundant among CD8 cells than CD4 cells; 3) VLA-4 stands out as an important parameter of differentiation both among CD4 cells and among CD8 cells. In short, our studies highlight and elucidate the relationships between adhesion, activation and differentiation.