MECHANISMS OF CELLULAR IMMUNE RESPONSES

我们的研究继续强调两个基本领域：1）识别 并表征细胞表面分子的功能， 促进T细胞识别;和2）分析 人类T细胞的亚群和这些亚群的功能能力 子集 使用流式细胞术，我们阐明了简化 关于两类分子表达变化的原理 在CD 4 T细胞发育过程中，这对T细胞粘附至关重要： 介导粘附的整合素和调节粘附的触发分子 这种粘合力。 在初始T细胞中， 整联蛋白α 3、α 4、α 5、α 6和β 1。 然而， 在记忆细胞中，存在一个或多个这样的增强表达， 整合素和显著的异质性。 在多个存储单元中 通过α 4和β 1的差异表达来区分亚群，我们 强调了对高α 4但低β 1亚群的研究 表情 多条证据表明这些代表了 肠道归巢细胞，特别是我们发现它们具有独特的高 整合素α 4 β 7的表达。 我们继续研究 CD 31分子具有调节T细胞粘附的独特能力。 CD 31显示在各种继发性免疫缺陷中T细胞表达的变化。 淋巴样组织和非淋巴样组织，这与 调节T细胞迁移。 此外，它对T细胞有多种作用， 活化，表明在T细胞和单核细胞活化中的作用。 最后，我们分析了参与T细胞增殖的早期信号事件， 活化以确定LFA-1/ICAM-1相互作用的贡献; 这些研究表明，它导致信号转导事件， 导致延长的磷脂酶C（PLC）活化和PIP 2 水解和[Ca 2 +]i水平的持续增加。

Our studies continue to 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. Using multicolor flow cytometry, we have elucidated simplifying principles regarding changes in expression of two classes of molecules during CD4 T cell development which are critical to T cell adhesion: integrins which mediate adhesion and trigger molecules which regulate that adhesion. Among naive T cells there is low homogenous expression of integrins alpha3, alpha4, alpha5, alpha6 and beta1. However, among memory cells there is augmented expression of one or more of these integrins and marked heterogeneity. Among the multiple memory cell subsets distinguished by differential expression of alpha4 and beta1, we have emphasized studies of a subset with high alpha4 but low beta1 expression. Multiple lines of evidence indicate that these represent gut-homing cells, especially our finding that they have uniquely high expression of the integrin alpha4beta7. We have continued our studies of the CD31 molecule with its unique capacity to regulate T cell adhesion. CD31 shows variation in expression of T cells in various secondary lymphoid tissue and nonlymphoid tissue, consistent with a role in regulating T cell migration. Further, it has multiple effects on T cell activation indicating a role in activation of both T cell and monocytes. Finally, we have analyzed early signaling events involved in T-cell activation to determine the contribution by LFA-l/ICAM-1 interaction; these studies demonstrate that it leads to signal transducing events resulting in prolonged phospholipase C (PLC) activation and PIP2 hydrolysis, and a sustained increase in [Ca2+]i level.