DEVELOPMENT & CONTROL OF NATURAL ANTOREACTIVE B T CELL

自身反应性α-βT细胞的产生机制 正常小鼠及其在免疫系统中的生理意义 还没有建立起来。我们之前曾报道过这一代 对自体细胞具有反应性的α-βT细胞是自然产生的 这样的细胞可以被鉴定为小的α-β-CD4+T细胞 胸腺中称为“胸腺0”的亚群。Thy0细胞迅速分泌一种 与自体细胞孵育时不同的细胞因子阵列， 尤其是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，因为这些细胞 如果适当的话，有可能影响免疫反应 激活了。我们最近的数据表明，NK1.1+αβ细胞，能够 TH2细胞的诱导和细胞毒性，可能代表着TH2的最终命运 这是0。然而，由于正在形成的共识是，NK1.1+ α-β细胞亚群代表第三个T细胞“谱系”，识别 非经典I类分子CD1作为配体，我们观察到 依赖于II类的细胞激活很难协调。因此， 我们建议研究自身反应性α-βT细胞的机制 Thy0和NK1.1+的发生和发育关系 α-βT细胞群。具体来说，我们将决定是否 自体反应性细胞的阳性选择原因很简单 该细胞具有中间的TCR亲和力/亲和力或相反的结果 来自一种在早期个体发育(AIM)期间运行的独特选择机制 1和20。此外，我们将确定NKαβ是否 自身反应性T细胞优先存活导致的细胞表型 受受体-配体介导的信号平衡的影响(目标3和 4)。这些调查包含了我们的长期目标，即了解 自然界的发育机制及其功能意义 免疫系统中的自体反应淋巴细胞。

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.