Laidlaw Brian J, Cui Weiguo, Amezquita Robert A, Gray Simon M, Guan Tianxia, Lu Yisi, Kobayashi Yasushi, Flavell Richard A, Kleinstein Steven H, Craft Joe, Kaech Susan M
Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
1] Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA. [2] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
Nat Immunol. 2015 Aug;16(8):871-9. doi: 10.1038/ni.3224. Epub 2015 Jul 6.
Memory CD8(+) T cells are critical for host defense upon reexposure to intracellular pathogens. We found that interleukin 10 (IL-10) derived from CD4(+) regulatory T cells (Treg cells) was necessary for the maturation of memory CD8(+) T cells following acute infection with lymphocytic choriomeningitis virus (LCMV). Treg cell-derived IL-10 was most important during the resolution phase, calming inflammation and the activation state of dendritic cells. Adoptive transfer of IL-10-sufficient Treg cells during the resolution phase 'restored' the maturation of memory CD8(+) T cells in IL-10-deficient mice. Our data indicate that Treg cell-derived IL-10 is needed to insulate CD8(+) T cells from inflammatory signals, and reveal that the resolution phase of infection is a critical period that influences the quality and function of developing memory CD8(+) T cells.
记忆性CD8(+) T细胞对于宿主再次接触细胞内病原体时的防御至关重要。我们发现，淋巴细胞性脉络丛脑膜炎病毒（LCMV）急性感染后，CD4(+) 调节性T细胞（Treg细胞）产生的白细胞介素10（IL-10）对于记忆性CD8(+) T细胞的成熟是必需的。Treg细胞来源的IL-10在疾病消退期最为重要，可减轻炎症以及树突状细胞的激活状态。在疾病消退期过继转移IL-10充足的Treg细胞可“恢复”IL-10缺陷小鼠中记忆性CD8(+) T细胞的成熟。我们的数据表明，需要Treg细胞来源的IL-10来使CD8(+) T细胞免受炎症信号的影响，并揭示感染的消退期是影响发育中的记忆性CD8(+) T细胞质量和功能的关键时期。
