Yang Y, Wilson J M
Institute for Human Gene Therapy, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.
Science. 1996 Sep 27;273(5283):1862-4. doi: 10.1126/science.273.5283.1862.
The role of CD40 ligand (CD40L) in the primary activation of T cells is not clear. The cellular and humoral immune responses to adenoviral vectors in a murine model of liver-directed gene transfer were studied to define the mechanisms responsible for CD40L-dependent T cell priming. CD40L-deficient mice did not develop effective cytotoxic T cells to transduced hepatocytes, and T cell-dependent B cell responses were absent. Full reconstitution of cellular and humoral immunity was achieved in CD40L-deficient mice by administration of an activating antibody to CD40 that increased expression of B7.2 on spleen cells. Wild-type mice could be made nonresponsive to vector by administration of antibodies to B7. Thus, CD40L-dependent activation of T cells occurs through signaling of CD40 in the antigen-presenting cell to enhance requisite costimulatory pathways that include B7.
CD40配体（CD40L）在T细胞的初始激活中的作用尚不清楚。我们研究了在肝脏定向基因转移的小鼠模型中对腺病毒载体的细胞免疫和体液免疫反应，以确定负责CD40L依赖性T细胞启动的机制。CD40L缺陷小鼠未产生针对转导肝细胞的有效细胞毒性T细胞，且不存在T细胞依赖性B细胞反应。通过给予一种激活CD40的抗体，该抗体增加了脾细胞上B7.2的表达，CD40L缺陷小鼠的细胞免疫和体液免疫得以完全重建。通过给予抗B7抗体，野生型小鼠可对载体无反应。因此，T细胞的CD40L依赖性激活是通过抗原呈递细胞中CD40的信号传导来增强包括B7在内的必需共刺激途径而发生的。
