Wallin J J, Liang L, Bakardjiev A, Sha W C
Immunology Division, Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
J Immunol. 2001 Jul 1;167(1):132-9. doi: 10.4049/jimmunol.167.1.132.
Although the recently identified ICOS/B7h costimulatory counterreceptors are critical regulators of CD4(+) T cell responses, their ability to regulate CD8(+) responses is unclear. Here we report using a tumor-rejection model that ectopic B7h expression can costimulate rejection by CD8(+) T cells in the absence of CD4(+) T cells. Although responses of naive T cells were significantly augmented by priming with B7h, B7h was surprisingly effective in mobilizing recall responses of adoptively transferred T cells. To explore why secondary responses of CD8(+) T cells were particularly enhanced by B7h, kinetics of ICOS up-regulation, proliferative responses, and cytokine production were compared from both naive and rechallenged 2C-transgenic T cells costimulated in vitro. Although B7h costimulated proliferative responses from both CD8(+) populations, rechallenged cells were preferentially costimulated for IL-2 and IFN-gamma production. These results indicate that ICOS/B7h counterreceptors likely function in vivo to enhance secondary responses by CD8(+) T cells.
尽管最近发现的ICOS/B7h共刺激反受体是CD4(+) T细胞反应的关键调节因子，但其调节CD8(+)反应的能力尚不清楚。在此我们报告，使用肿瘤排斥模型，在没有CD4(+) T细胞的情况下，异位表达B7h可共刺激CD8(+) T细胞介导的排斥反应。虽然用B7h致敏可显著增强初始T细胞的反应，但令人惊讶的是，B7h在动员过继转移T细胞的回忆反应方面非常有效。为了探究为什么B7h特别增强了CD8(+) T细胞的二次反应，我们比较了体外共刺激的初始和再次攻击的2C转基因T细胞的ICOS上调动力学、增殖反应和细胞因子产生情况。虽然B7h共刺激了两个CD8(+)群体的增殖反应，但再次攻击的细胞在产生IL-2和IFN-γ方面更优先受到共刺激。这些结果表明，ICOS/B7h反受体可能在体内发挥作用，以增强CD8(+) T细胞的二次反应。
