Meek Stephanie M, Williams Matthew A
Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA.
Pathogens. 2018 Feb 13;7(1):22. doi: 10.3390/pathogens7010022.
While CD8⁺ memory T cells can promote long-lived protection from secondary exposure to intracellular pathogens, less is known regarding the direct protective mechanisms of CD4⁺ T cells. We utilized a prime/boost model in which mice are initially exposed to an acutely infecting strain of lymphocytic choriomeningitis virus (LCMV), followed by a heterologous rechallenge with recombinantly expressing the MHC Class II-restricted LCMV epitope, GP (Lm-gp61). We found that heterologous Lm-gp61 rechallenge resulted in robust activation of CD4⁺ memory T cells and that they were required for rapid bacterial clearance. We further assessed the relative roles of TNF and IFNγ in the direct anti-bacterial function of CD4⁺ memory T cells. We found that disruption of TNF resulted in a complete loss of protection mediated by CD4⁺ memory T cells, whereas disruption of IFNγ signaling to macrophages results in only a partial loss of protection. The protective effect mediated by CD4⁺ T cells corresponded to the rapid accumulation of pro-inflammatory macrophages in the spleen and an altered inflammatory environment in vivo. Overall, we conclude that protection mediated by CD4⁺ memory T cells from heterologous challenge is most directly dependent on TNF, whereas IFNγ only plays a minor role.
虽然CD8⁺记忆T细胞可促进对再次接触细胞内病原体的长期保护，但关于CD4⁺T细胞的直接保护机制，人们了解较少。我们采用了一种初免/加强模型，即小鼠首先接触急性感染性淋巴细胞性脉络丛脑膜炎病毒（LCMV）毒株，随后用重组表达MHC II类限制性LCMV表位GP（Lm-gp61）进行异源再次攻击。我们发现，异源Lm-gp61再次攻击导致CD4⁺记忆T细胞的强劲激活，且它们是快速清除细菌所必需的。我们进一步评估了TNF和IFNγ在CD4⁺记忆T细胞直接抗菌功能中的相对作用。我们发现，TNF的缺失导致CD4⁺记忆T细胞介导的保护作用完全丧失，而巨噬细胞中IFNγ信号传导的缺失仅导致部分保护作用丧失。CD4⁺T细胞介导的保护作用与脾脏中促炎性巨噬细胞的快速积累以及体内炎症环境的改变相对应。总体而言，我们得出结论，CD4⁺记忆T细胞介导的针对异源攻击的保护作用最直接依赖于TNF，而IFNγ仅起次要作用。
