DISTINCT T CELL ACTIVATION BY ANTIGEN PRESENTING CELLS

其他致敏半抗原在紫外线照射中的应用 皮肤诱导T细胞介导的免疫耐受。沿着其他 皮肤环境的变化，抗原呈递细胞的改变 (APC)紫外线照射后，表皮中的细胞群发生变化。6到72岁 紫外线照射后24小时，浸润性巨噬细胞（UV-Mph）取代了 正常的固有树突状APC，朗格汉斯细胞，作为主要的 表皮APC。这些UV-Mph已被证明可以诱导抗原 小鼠中的特异性耐受性，并与人类中的耐受性相关。 驱动我的工作的基本假设是，这两个APC，LC和UV- Mph，与不同的免疫结果有关， 致敏和耐受分别激活T细胞， 不同的方式。 拟议的研究将确定是否存在差异， LC和UV-Mph之间存在共刺激分子，如果是这样， 这些参与了T细胞的不同激活状态， 它们相互作用。 因此，流式细胞术分析的相对 UV-Mph法检测B7-1、B7-2、CD 40、VCAM-1和纤连蛋白的表达， 将进行LC。差异的功能意义将 通过确定以下物质对T细胞活化的影响来探索： 改变这些分子或其受体的表达的操作， 发送或接收信号的能力。待测量的T细胞效应 是通过流式细胞术的IL-2 Ra（CD 25）表达，通过氚标记的流式细胞术的生长， 胸苷掺入和细胞因子产生（IL-2，IL-4，IL-5， IFN-g）。 系统的操作将增加 重组细胞因子以改变共刺激分子表达， 阻断针对共刺激分子或其T细胞配体的抗体， 以及添加针对候选生长因子的中和抗体 (lL-2、IL-4、IL-7和IL-15）。 预期的结果是，以前发表的差异，在T 细胞CD 25表达是由于共刺激因子的不同利用， 分子。这些差异也导致了不同的T细胞生长 因子使用和细胞因子产生。

Application of otherwise sensitizing haptens to ultraviolet irradiated skin induces T cell-mediated immunologic tolerance. Along with other changes in the cutaneous milieu, alterations in antigen presenting cell (APC) populations in the epidermis occur after UV exposure. Six to 72 hours after UV exposure, infiltrating macrophages (UV-Mph) replace the normal, indigenous dendritic APC, Langerhans cells, as the predominant APC of epidermis. These UV-Mph have been shown to induce antigen specific tolerance in mice and are associated with tolerance in humans. The basic hypothesis driving my work is that these two APC, LC and UV- Mph, which are associated with the distinct immune outcomes of sensitization and tolerization, respectively, activate T cells in distinct ways. The proposed research will determine whether differences in costimulatory molecules exist between LC and UV-Mph, and if so, whether these are involved in distinct activational states of the T cells with which they interact. Thus, flow cytometric analysis of the relative expression of B7-1, B7-2, CD40, VCAM-1 and fibronectin by UV-Mph and LC will be performed. The functional significance of differences will be explored by determining the effect on T cell activation of manipulations that alter the expression of these molecules or their ability to send or receive signals. The T cell effects to be measured are lL-2Ra (CD25) expression by flow cytometry, growth by tritiated thymidine incorporation, and cytokine production (IL-2, IL-4, IL-5, IFN-g) by ELISPOT. Manipulations of the system are to be addition of recombinant cytokines to alter costimulatory molecule expression, blocking antibodies to costimulatory molecules or their T cell ligands, and addition of neutralizing antibodies to candidate growth factors (lL-2, lL-4, lL-7 and IL-15). The expected results are that previously published differences in T cell CD25 expression are due to different utilization of costimulatory molecules. These differences also lead to different T cell growth factor use and cytokine production after activation by these two APC.