Systemic C3 Modulates CD8+ T Cell Contraction after Listeria monocytogenes Infection
Systemic C3 Modulates CD8+ T Cell Contraction after Listeria monocytogenes Infection
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DOI：
10.4049/jimmunol.1302763
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发表时间：
2014-10
期刊：
影响因子：
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通讯作者：
Yulong Tan;Yongsheng Li;Xiao-lan Fu;Fei Yang;P. Zheng;Jue Zhang;Bo Guo;Yuzhang Wu
中科院分区：
文献类型：
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作者：
Yulong Tan;Yongsheng Li;Xiao-lan Fu;Fei Yang;P. Zheng;Jue Zhang;Bo Guo;Yuzhang Wu
在感染消退后发生的Ag特异性CD 8 + T细胞收缩（收缩）对于免疫系统的稳态至关重要。尽管补体成分调节初级CD 8 + T细胞反应，但没有足够的证据支持它们在调节收缩和记忆方面的作用。在这项研究中，我们发现，C3缺陷（C3−/−）小鼠表现出显着减少CD 8 + T细胞收缩比野生型小鼠感染后表达OVA的重组单核细胞增生李斯特菌。动力学分析还显示，用眼镜蛇毒因子处理以消耗C3的小鼠收缩减少，这与移植来自与野生型受体小鼠相同供体的骨髓细胞的C3−/−受体小鼠的结果一致。与野生型小鼠相比，C3−/−小鼠产生的记忆细胞的表型没有改变。此外，C3下游的C5 aR信号传导不参与收缩的调节。此外，C3对收缩的调节可能不依赖于抗原刺激的持续时间或效应CD 8 + T细胞的功能亲合力。然而，C3−/−小鼠收缩减少伴随着KLRG-1hi（免疫细胞凝集素样受体G1）CD 127 lo短寿命效应细胞在反应高峰期的比例下降，并与感染后早期产生的炎性细胞因子（如IL-12和IFN-γ）水平下降相关。这些结果为系统性C3在细胞内细菌感染后调节收缩的作用提供了新的见解，并可能有助于开发更有效的疫苗。
Ag-specific CD8+ T cell contraction (contraction), which occurs after the resolution of infection, is critical for homeostasis of the immune system. Although complement components regulate the primary CD8+ T cell response, there is insufficient evidence supporting their role in regulating contraction and memory. In this study, we show that C3-deficient (C3−/−) mice exhibited significantly less CD8+ T cell contraction than did wild-type mice postinfection with recombinant Listeria monocytogenes expressing OVA. Kinetic analyses also revealed decreased contraction in mice treated with cobra venom factor to deplete C3, which was consistent with the results in C3−/− recipient mice transplanted with bone marrow cells from the same donors as wild-type recipient mice. The phenotypes of memory cells generated by C3−/− mice were not altered compared with those of wild-type mice. Further, C5aR signaling downstream of C3 was not involved in the regulation of contraction. Moreover, the regulation of contraction by C3 may be independent of the duration of antigenic stimulation or the functional avidity of effector CD8+ T cells. However, reduced contraction in C3−/− mice was accompanied by a decrease in the proportion of KLRG-1hi (killer-cell lectin-like receptor G1) CD127lo short-lived effector cells at the peak of the response and correlated with a reduction in the levels of inflammatory cytokines, such as IL-12 and IFN-γ, produced early postinfection. These results provide new insights into the role of systemic C3 in regulating contraction following intracellular bacterial infection and may help to develop vaccines that are more effective.