MECHANISMS OF CELLULAR IMMUNE RESPONSES

我们对长期存在的关于生理学和 淋巴结T细胞依赖区的构筑，并进化成 通过结合体内免疫组织学更丰富的了解 示踪研究和细胞培养。首先，在T细胞依赖区 T细胞在高度组织化的迷宫中迁移。它的拓扑结构 迷宫为有效的细胞接触进行了优化：a)窄水 B)由富含细胞外基质的基质细胞排列的通道 适用于为细胞迁移提供牵引力，以及c)通过 特异性抗原提呈交指树突状细胞(IDC) 用来呈递抗原。第二，有一个有效的 网状内皮细胞屏障将这个隔膜与 淋巴/鼻窦。第三，可溶性示踪剂从淋巴中的移动 进入T细胞依赖区是通过沿 史无前例的管道系统由非常基质细胞包裹 形成迷宫的墙壁。第四，间质细胞似乎 通过产生它们自己的细胞来调节淋巴结的环境 可溶性因子如TGFb，趋化因子如IL-8和MCP-1。 了解这些特征对于治疗以下疾病很重要 免疫反应不足(如癌症)或夸大(如 如关节炎和糖尿病)。此外，在最初的体外研究中，我们 发现淋巴结基质细胞显著促进T细胞感染 被HIV病毒感染。我们正在研究细胞的形态和生化 淋巴细胞迁移的过程，特别强调 丝状伪足。 我们正在系统地鉴定人类和小鼠的外周血液 子集来理解表面分子的集合 每个人。总体而言，在生物学领域需要更好的策略。 社区来组织关于人类蛋白质的大量信息；我们正在 开发一种国际资源，我们将其命名为Prow[蛋白质 网上评论]来帮助解决这个问题。

We have questioned longstanding dogmas regarding the physiology and architecture of T-cell dependent area of lymph nodes, and evolved a much richer understanding by a combination of immunohistology, in vivo tracer studies, and cell culture. First, in the T-cell-dependent area T cells migrate in a highly organized labyrinth. The topology of that labyrinth is optimized for efficient cell contact: a) narrow aqueous channels lined b) by stromal cells rich in extracellular matrix suitable for providing traction for cell migration and c) by antigen-presenting interdigitating dendritic cells (IDC) specialized for presenting antigen. Second, there is an effective reticulo-endothelial cell barrier which isolates this compartment from the lymph/sinuses. Third, the movement of soluble tracers from lymph into the T cell dependent areas occurs by transport along an unprecedented conduit system ensheathed by the very stromal cells that form the walls of the labyrinth. Fourth, the stromal cells appear to condition the environment of the lymph node by producing their own soluble factors such as TGFb, and chemokines such as IL-8 and MCP-1. Understanding these features is important to treating diseases where immune responses are deficient (such as cancers) or exaggerated (such as arthritis and diabetes). Moreover, in initial in vitro studies, we find that lymph node stromal cells markedly facilitate T cell infection by HIV virus. We are investigating the morphological and biochemical processes whereby lymphocytes migrate, with particular emphasis on filopodia. We are systematically characterizing human and mouse peripheral blood subsets to understand the ensemble of surfaces molecules expressed by each. In general, better strategies will be required in the biological community to organize the mass of information on human proteins; we are developing an international resource which we designate PROW [Protein Reviews on the Web] to help address this problem.