DEVELOPMENT & CONTROL OF NATURAL ANTOREACTIVE B T CELL

免疫缺陷综合征中自身反应性α β T细胞的产生机制 正常小鼠及其在免疫系统中的生理意义 尚未建立。 我们以前曾报道过， 对自体细胞具有反应性的α β T细胞自然产生 并且这种细胞可以被鉴定为小α β CD 4 + T细胞 在胸腺中称为“Thy 0”。 Thy 0细胞迅速分泌一种 在与自体细胞孵育后产生多种细胞因子， 特别是II+类细胞。 理解发展机制 这种自身反应性T细胞的命运很重要， 有可能影响免疫反应，如果适当的话， 激活 我们最近的数据表明，NK1.1+ α β细胞，能够 TH 2细胞诱导和细胞毒性，可能代表了最终的命运， Thy0. 然而，由于有一个新兴的共识，即NK1.1+ α β细胞亚群代表第三种T细胞“谱系”， 非经典I类分子CD 1作为配体，我们观察到 II类依赖性细胞活化难以调和。 因此，我们认为， 我们建议研究自身反应性α β T细胞的机制， Thy 0与NK1.1+的世代发育关系 α β T细胞群。 具体而言，我们将解决 自身反应性细胞的阳性选择被简单地解释， 细胞具有中等TCR亲和力/亲合力，或者相反导致 从一个独特的选择机制运作在早期个体发育（目的 1和20。 此外，我们将确定NK α β是否 自身反应性T细胞的优先存活导致细胞表型 受受体-配体介导的信号平衡的影响（Aim 3和 4）。 这些调查涵盖了我们的长期目标， 自然生态系统发育机制及其功能意义 免疫系统中的自身反应性淋巴细胞。

The mechanism for generation of autoreactive alpha beta T cells in normal mice and their physiological significance in the immune system are not yet established. We have previously reported that generation of alpha beta T cells with reactivity to autologous cells occurs naturally and that such cells can be identified as a small alpha beta CD4+ T cell subset, termed "Thy0" in the thymus. Thy0 cells promptly secrete a diverse array of cytokines upon incubation with autologous cells, particularly class II+ cells. Understanding the developmental mechanism and the fate of such autoreactive T cells is important since these cells have the potential to influence the immune response if appropriately activated. Our recent data suggest that NK1.1+ alpha beta cells, capable of TH2 cell induction and cytotoxicity, may represent the ultimate fate of Thy0. However, since there is an emerging consensus that the NK1.1+ alpha beta cell subset represents a third T cell "lineage", recognizing the non-classical class I molecule CD1 as a ligand, our observation of class II dependent cell activation is difficult to reconcile. Therefore, we propose to investigate the mechanism of autoreactive alpha beta T cell generation and developmental relationship between Thy0 and NK1.1+ alpha beta T cell populations. Specifically, we will resolve whether the positive selection of autoreactive cells is accounted for simply because the cell possesses an intermediate TCR affinity/avidity or instead results from a unique selection mechanism operating during early ontogeny (Aim 1 and 20. Furthermore, we will determine whether the NK alpha beta cell phenotype results from preferential survival of autoreactive T cells influenced by a balance of receptor-ligand mediated signals (Aim 3 and 4). These investigations encompass our long-term goal to understand the developmental mechanism and functional significance of natural autoreactive lymphocytes in the immune system.