Department of Microbiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511, Japan.
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center-Shreveport (LSUHSC-S), 1501 Kings Highway, Shreveport, LA 71130, USA.
Sci Rep. 2017 Sep 5;7(1):10496. doi: 10.1038/s41598-017-10980-0.
Intracerebral Theiler's murine encephalomyelitis virus (TMEV) infection in mice induces inflammatory demyelination in the central nervous system. Although C57BL/6 mice normally resistant to TMEV infection with viral clearance, we have previously demonstrated that RORγt-transgenic (tg) C57BL/6 mice, which have Th17-biased responses due to RORγt overexpression in T cells, became susceptible to TMEV infection with viral persistence. Here, using T-bet-tg C57BL/6 mice and Gata3-tg C57BL/6 mice, we demonstrated that overexpression of T-bet, but not Gata3, in T cells was detrimental in TMEV infection. Unexpectedly, T-bet-tg mice died 2 to 3 weeks after infection due to failure of viral clearance. Here, TMEV infection induced splenic T cell depletion, which was associated with lower anti-viral antibody and T cell responses. In contrast, Gata3-tg mice remained resistant, while Gata3-tg mice had lower IFN-γ and higher IL-4 production with increased anti-viral IgG1 responses. Thus, our data identify how overexpression of T-bet and Gata3 in T cells alters anti-viral immunity and confers susceptibility to TMEV infection.
脑内 Theiler's 小鼠脑脊髓炎病毒（TMEV）感染可诱导中枢神经系统的炎症性脱髓鞘。虽然 C57BL/6 小鼠通常对 TMEV 感染具有抵抗力，可清除病毒，但我们之前已证明，由于 T 细胞中 RORγt 过表达导致 Th17 偏向反应的 RORγt 转基因（tg）C57BL/6 小鼠易受 TMEV 感染且病毒持续存在。在这里，我们使用 T-bet-tg C57BL/6 小鼠和 Gata3-tg C57BL/6 小鼠，证明 T 细胞中 T-bet 的过表达而非 Gata3 的过表达在 TMEV 感染中是有害的。出乎意料的是，T-bet-tg 小鼠在感染后 2 至 3 周因未能清除病毒而死亡。在这里，TMEV 感染诱导脾 T 细胞耗竭，这与较低的抗病毒抗体和 T 细胞反应有关。相比之下，Gata3-tg 小鼠仍具有抗性，而 Gata3-tg 小鼠具有较低的 IFN-γ 和较高的 IL-4 产生，以及增加的抗病毒 IgG1 反应。因此，我们的数据确定了 T 细胞中 T-bet 和 Gata3 的过表达如何改变抗病毒免疫并赋予对 TMEV 感染的易感性。
