Howland K C, Ausubel L J, London C A, Abbas A K
Immunology Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
J Immunol. 2000 May 1;164(9):4465-70. doi: 10.4049/jimmunol.164.9.4465.
Costimulation of T cell activation involves both the B7:CD28 as well as the CD40 ligand (CD40L):CD40 pathway. To determine the importance of these pathways to in vitro and in vivo T cell activation, a direct comparison was made of the responses of TCR transgenic T cells lacking either CD28 or CD40L. In vitro, CD28-/- T cells showed a greater reduction in proliferative responses to Ag than did CD40L-/- T cells. The absence of CD28 resulted in defective Th2 responses, whereas CD40L-/- T cells were defective in Th1 development. In vivo, CD28-/- T cells failed to expand upon immunization, whereas CD40L-/- T cells could not sustain a response. These results suggest that CD28 is critical for initiating T cell responses, whereas CD40L is required for sustained Th1 responses. The different functional roles of these costimulatory pathways may explain why blocking B7:CD28 and CD40L:CD40 interactions has an additive effect in inhibiting T cell responses.
T细胞激活的共刺激涉及B7:CD28以及CD40配体(CD40L):CD40途径。为了确定这些途径对体外和体内T细胞激活的重要性，对缺乏CD28或CD40L的TCR转基因T细胞的反应进行了直接比较。在体外，与CD40L-/- T细胞相比，CD28-/- T细胞对抗原的增殖反应降低得更多。CD28的缺失导致Th2反应缺陷，而CD40L-/- T细胞在Th1发育方面存在缺陷。在体内，CD28-/- T细胞在免疫后未能扩增，而CD40L-/- T细胞无法维持反应。这些结果表明，CD28对启动T细胞反应至关重要，而CD40L是持续Th1反应所必需的。这些共刺激途径的不同功能作用可能解释了为什么阻断B7:CD28和CD40L:CD40相互作用在抑制T细胞反应方面具有累加效应。
