Quddus J, Kaplan A, Richardson B C
Department of Medicine, University of Michigan, Ann Arbor.
Immunology. 1994 Jun;82(2):301-5.
The process of thymic maturation permits development of T cells expressing receptors which recognize self-major histocompatibility complex (MHC) determinants, but deletes T cells recognizing self-MHC determinants with high affinity. This selection process is evolutionarily conserved, and presumably serves in part to prevent the release of autoreactive cells. However, the mechanisms involved in the selection process, and the molecules required are incompletely characterized. Lymphocyte function-associated antigen-1 (LFA-1) is an accessory molecule important in T-cell activation, is involved in thymocyte-epithelial cell binding, and contributes to the maturation of CD4-CD8- thymocytes to the CD4+CD8+ stage. In this report we have investigated whether LFA-1 also contributes to the thymic deletion of potentially self-reactive cells. Neonatal C57Br mice were injected with amounts of a monoclonal antibody to LFA-1 that saturated thymic binding sites, then splenocytes were examined for T cells expressing receptors normally deleted in the thymus. The results demonstrate that V beta 17a+ T cells, normally deleted in this strain, can be detected in the spleen following administration of anti-LFA-1, thus supporting the hypothesis that LFA-1 also contributes to negative selection. The potential significance of LFA-1 involvement in multiple thymic maturation events is discussed.
胸腺成熟过程允许表达识别自身主要组织相容性复合体（MHC）决定簇的受体的T细胞发育，但会删除高亲和力识别自身MHC决定簇的T细胞。这种选择过程在进化上是保守的，大概部分用于防止自身反应性细胞的释放。然而，参与选择过程的机制以及所需的分子尚未完全明确。淋巴细胞功能相关抗原-1（LFA-1）是T细胞激活中重要的辅助分子，参与胸腺细胞与上皮细胞的结合，并有助于CD4-CD8-胸腺细胞向CD4+CD8+阶段成熟。在本报告中，我们研究了LFA-1是否也有助于胸腺中潜在自身反应性细胞的清除。给新生C57Br小鼠注射能饱和胸腺结合位点的抗LFA-1单克隆抗体，然后检查脾细胞中表达通常在胸腺中被清除的受体的T细胞。结果表明，在该品系中通常被清除的Vβ17a+T细胞在给予抗LFA-1后可在脾脏中被检测到，从而支持了LFA-1也有助于阴性选择的假说。文中讨论了LFA-1参与多个胸腺成熟事件的潜在意义。
