MECHANISMS OF CELLULAR IMMUNE RESPONSES

我们的研究强调两个基本领域：1）表征细胞 促进T细胞识别的表面分子;和2）分析 人T细胞亚群之间的异质性和功能性T细胞亚群之间的异质性 这些子集的能力。 在了解 T细胞与内皮细胞相互作用的分子基础。 两个新 分子途径正在被阐明。 记忆T细胞的一个亚群 与内皮细胞上的可诱导配体ELAM-1;由于该途径 不需要预先激活T细胞，这可能是最重要的 在记忆T细胞最初附着于炎症内皮细胞的过程中， vivo. 我们已经定义了分子CD 31的许多特征， 这使得它成为一个非常有吸引力的候选人， 调节T细胞与内皮的粘附。 CD 31不仅介导 粘附，但它也强烈地诱导粘附的多重 存在但相对不粘附在静息T细胞上整合素 细胞 T细胞通过三种其他分子与内皮细胞相互作用 途径：VLA-4/VCAM 1、LFA-1/ICAM-1和LFA-1/ICAM-2也已被研究。 系统分析。 不仅是CD 3和CD 31， 表面分子CD 7和CD 28可以增强粘附功能， 由T细胞表达的多种整合素。 此外，粘附分子 调节T细胞活化，如我们最近的研究所示， VLA-4/VCAM-1，其证实并扩展了正在进行的LFA-1/ICAM-1的研究 交互. 表型异质性的详细分析 外周血CD 4 + T细胞，以及最近的CD 8 + T细胞， 表面表型调节的显著复杂性，例如：1）CD 4 存储器单元可以基于定量的 CD 45 RB亚型表达的差异; 2）记忆细胞似乎 在CD 8细胞中的丰度比CD 4细胞低得多; 3）VLA-4突出 作为CD 4细胞之间分化的重要参数， CD 8细胞。 简而言之，我们的研究强调并阐明了 粘附、活化和分化之间的关系。

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.