German Cancer Research Center, Heidelberg, Germany.
J Immunol. 2010 Mar 15;184(6):2855-62. doi: 10.4049/jimmunol.0902708. Epub 2010 Feb 17.
IFN-gamma regulates multiple processes in the immune system. Although its antimicrobial effector functions are well described, less is known about the mechanisms by which IFN-gamma regulates CD8(+) T cell homeostasis. With the help of adoptive T cell transfers, we show in this study that IFN-gammaR signaling in CD8(+) T cells is dispensable for expansion, contraction, and memory differentiation in response to peptide vaccination. In contrast, host IFN-gammaR signaling counterregulates CD8(+) T cell responses and the generation of effector memory T cell processes, which are partially regulated by CD11b(+) cells. Similar to vaccination-induced proliferation, host IFN-gammaR signaling limits the expansion of naive CD8(+) T cells and their differentiation into effector memory-like T cells in lymphopenic mice. In contrast to peptide vaccination, IFN-gammaR signaling in CD8(+) T cells contributes to memory fate decision in response to lymphopenia, an effect that is fully reversed by high-affinity TCR ligands. In conclusion, we show that host IFN-gammaR signaling controls the magnitude of CD8(+) T cell responses and subsequent memory differentiation under lymphopenic and nonlymphopenic conditions. In contrast, IFN-gammaR signaling in CD8(+) T cells does not affect cell numbers under either condition, but it directs memory fate decision in response to weak TCR ligands.
IFN-γ 调节免疫系统中的多种过程。尽管其抗微生物效应功能已得到很好的描述，但对于 IFN-γ 如何调节 CD8(+)T 细胞稳态的机制知之甚少。在本研究中，我们通过过继性 T 细胞转移表明，CD8(+)T 细胞中的 IFN-γR 信号对于肽疫苗接种引起的扩增、收缩和记忆分化是可有可无的。相比之下，宿主 IFN-γR 信号会拮抗 CD8(+)T 细胞反应和效应记忆 T 细胞过程的产生，而这部分过程受 CD11b(+)细胞调节。与疫苗接种诱导的增殖类似，宿主 IFN-γR 信号限制了淋巴减少小鼠中幼稚 CD8(+)T 细胞的扩增及其分化为效应记忆样 T 细胞的过程。与肽疫苗接种不同，CD8(+)T 细胞中的 IFN-γR 信号有助于对淋巴减少做出记忆命运决定，而高亲和力 TCR 配体则完全逆转了这一效应。总之，我们表明，宿主 IFN-γR 信号控制了淋巴减少和非淋巴减少条件下 CD8(+)T 细胞反应的幅度及其随后的记忆分化。相比之下，CD8(+)T 细胞中的 IFN-γR 信号在两种情况下均不影响细胞数量，但它指导对弱 TCR 配体的记忆命运决定。
