MECHANISMS OF CELLULAR IMMUNE RESPONSES

我们对人类T细胞识别的研究强调了两个基本方面：1) 细胞表面分子功能的鉴定与表征 这有助于T细胞识别；以及2)分析 人类T细胞亚群和这些亚群的功能能力。 T细胞与细胞外基质相互作用的主要新发现 (ECM)组件。静息T细胞表面表达三个成员 VLA(Beta1)整合素家族并可通过三种不同的方式与ECM黏附 VLA介导的通路有：VLA-4/纤维连接蛋白、VLA-5/纤维连接蛋白、VLA-6/层粘连蛋白。 通过这些途径的结合受两个截然不同且互补的 机制：1)VLA受体的表达受T细胞调控 分化；2)受体的功能容量迅速 受监管的。因为我们发现这些受体也促进了 T细胞在体外，它们可能不仅在T细胞中重要 黏附/迁移，也参与T细胞的活化。实现以下目标的机制 对粘附性的监管正在调查中；一种可能性是 探索的是快速激活诱导细胞表面脱落 分子调节T细胞的黏附。同时进行的研究延长了我们的 理解涉及其他附件的通路的重要性 促进T细胞活化的分子。T细胞的系统分析 LFA-1与生化纯化的配体ICAM-1的相互作用强调 这种分子相互作用作为T细胞共刺激因子的有效作用 激活。此外，单核细胞在体内的共刺激作用分析 T细胞受体介导的激活显示出重要的贡献 不仅是LFA-I/ICAM-1，而且还有CD2/LFA-3和其他目前在 调查。新的T细胞亚群已经被定义为mAb特异性的 CD45RB抗原。此标记允许区分两个子集 记忆T细胞，其功能能力正在研究中。 多种分子在细胞表面表达的系统定量分析 正常人和艾滋病患者T细胞表面继续发现新的 T细胞亚群的异质性，其生理相关性现在是 调查过了。

Our studies of human T cell recognition emphasize two fundamental areas: 1) identifying and characterizing the functions of 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. Major new findings relate to T cell interaction with extracellular matrix (ECM) components. Resting T cells express on their surface three members of the VLA (beta1) integrin family and can adhere to ECM via three distinct VLA-mediated pathways: VLA-4/fibronectin, VLA-5/fibronectin, VLA-6/laminin. Binding via these pathways is regulated by two distinct and complementary mechanisms: 1) Expression of the VLA receptors is regulated with T cell differentiation; 2) the functional capacity of the receptors is rapidly regulated. Since we find that these receptors also facilitate activation of the T cells in vitro, they may be important not only in T cell adhesion/migration, but also in T cell activation. The mechanisms for regulation of adhesion are under investigation; one possibility being explored is that rapid activation-induced shedding of cell surface molecules modulates T cell adhesion. Concurrent studies have extended our understanding of the importance of pathways involving other accessory molecules in facilitating T cell activation. Systematic analyses of T cell LFA-1 interaction with biochemically purified ligand ICAM-1 emphasize the potent role of this molecular interaction as a costimulus for T cell activation. Furthermore, analysis of the costimulatory role of monocytes in T-cell receptor-mediated activation demonstrate important contributions not only of LFA-I/ICAM-1 but also CD2/LFA-3 and other molecules currently under investigation. New subsets of T cells have been defined with a mAb specific for the CD45RB antigen. This marker allows discrimination of two subsets of memory T cells, whose functional capacities are under investigation. Systematic quantitative analysis of expression of many molecules on the surface of T cells from normals and AIDS patients continue to reveal new heterogeneity of T cell subsets, whose physiological relevance is now being investigated.