CD40 preferentially costimulates activation of CD4+ T lymphocytes.
CD40 preferentially costimulates activation of CD4+ T lymphocytes.
复制标题
CD40 优先共刺激 CD4 T 淋巴细胞的激活。
作者：
M. Cayabyab;J. Phillips;L. Lanier
CD40是一种表达于B细胞表面的膜分化抗原，与抗CD40单抗或新近发现的CD40配体(CD40L)结合后，可诱导B细胞生长和Ig合成。T细胞经抗CD3单抗或有丝分裂原激活后，可迅速诱导CD40L表达。虽然CD40-CD40L的相互作用显然对B细胞有利，但我们推测T细胞的互惠共刺激也可能发生。我们已经使用基因转染法证明了人类小的静止T细胞与CD40+的小鼠转染体之间的相互作用显著增强了抗CD3诱导的T细胞的增殖并导致CTL的产生。CD40共刺激的T细胞增殖依赖于IL-2。CD40+共刺激T细胞增殖的能力是特异的，因为同一宿主细胞中的VCAM-1+、CD54+、CD72+、CD56+、CD31+和Fas+的转染物是不活跃的。CD4+T细胞优先对CD40共刺激反应，而CD8+T细胞反应较弱。相比之下，与B7共刺激基因在CD4+和CD8+T细胞亚群中诱导了等量的增殖。此外，成人幼稚T细胞和记忆性T细胞以及脐带血T细胞对CD40也有反应。这些发现表明，CD40-CD40L共刺激通路可能允许在与携带CD40的APC相互作用后选择性地扩增CD4+T细胞。CD40在APC以及髓质和胸腺皮质上的表达相对有限，提示这种相互作用可能在T细胞分化和激活中发挥作用。
CD40 is a membrane differentiation antigen constitutively expressed on B cells that induces B cell growth and Ig synthesis after ligation with anti-CD40 mAb or with the recently identified CD40 ligand (CD40L). CD40L is rapidly induced on T cells after activation with anti-CD3 mAb or mitogens. While CD40-CD40L interactions are clearly beneficial to B cells, we speculated that a reciprocal costimulation of T cells might also occur. We have used genetic transfection to demonstrate that interactions between human small, resting T cells and CD40+ murine transfectants substantially augmented anti-CD3 induced T cell proliferation and resulted in the generation of CTL. T cell proliferation costimulated by CD40 was IL-2 dependent. The ability of CD40+ transfectants to costimulate T cell proliferation was specific in that VCAM-1+, CD54+, CD72+, CD56+, CD31+, and fas+ transfectants in the same host cells were inactive. CD4+ T cells preferentially responded to CD40 costimulation, whereas CD8+ T cells were substantially less reactive. By contrast, costimulation with B7 transfectants induced equivalent proliferation in the CD4+ and CD8+ T cell subsets. In addition, adult naive and memory T cells, as well as cord blood T cells, were responsive to CD40. These findings suggest that the CD40-CD40L costimulation pathway may allow for selective expansion of CD4+ T cells after interaction with CD40-bearing APC. The relatively restricted expression of CD40 on APC, as well as on medullary and cortical thymic epithelium, indicates a possible role for this interaction in T cell differentiation and activation.