Haring Jodie S, Corbin Gail A, Harty John T
Department of Microbiology, University of Iowa, Iowa City, 52242, USA.
J Immunol. 2005 Jun 1;174(11):6791-802. doi: 10.4049/jimmunol.174.11.6791.
IFN-gamma plays a critical role in the CD8(+) T cell response to infection, but when and if this cytokine directly signals CD8(+) T cells during an immune response is unknown. We show that naive Ag-specific CD8(+) T cells receive IFN-gamma signals within 12 h after in vivo infection with Listeria monocytogenes and then become unresponsive to IFN-gamma throughout the ensuing Ag-driven expansion phase. Ag-specific CD8(+) T cells regain partial IFN-gamma responsiveness throughout the contraction phase, whereas the memory pool exhibits uniform, but reduced, responsiveness that is also modulated during the secondary response. The responsiveness of Ag-specific CD8(+) T cells to IFN-gamma correlated with modulation in the expression of IFN-gammaR2, but not with IFN-gammaR1 or suppressor of cytokine signaling-1. This dynamic regulation suggests that early IFN-gamma signals participate in regulation of the primary CD8(+) T cell response program, but that evading or minimizing IFN-gamma signals during expansion and the memory phase may contribute to appropriate regulation of the CD8(+) T cell response.
干扰素-γ在CD8(+) T细胞对感染的应答中起关键作用，但在免疫应答过程中该细胞因子是否以及何时直接向CD8(+) T细胞发出信号尚不清楚。我们发现，用单核细胞增生李斯特菌进行体内感染后12小时内，初始抗原特异性CD8(+) T细胞会接收干扰素-γ信号，然后在随后的抗原驱动的扩增阶段对干扰素-γ不再有反应。抗原特异性CD8(+) T细胞在整个收缩阶段恢复部分干扰素-γ反应性，而记忆库表现出均匀但降低的反应性，在二次应答期间也受到调节。抗原特异性CD8(+) T细胞对干扰素-γ的反应性与干扰素-γR2表达的调节相关，但与干扰素-γR1或细胞因子信号传导抑制因子-1无关。这种动态调节表明，早期干扰素-γ信号参与了初始CD8(+) T细胞应答程序的调节，但在扩增和记忆阶段逃避或最小化干扰素-γ信号可能有助于对CD8(+) T细胞应答进行适当调节。
