Journal Article T-bet, but not Gata3, overexpression is detrimental in a neurotropic viral infection

Sato, Fumitaka  ,  Kawai, Eiichiro  ,  Martinez, Nicholas E.  ,  Omura, Seiichi  ,  Park, Ah-Mee  ,  Takahashi, Satoru  ,  Yoh, Keigyou  ,  Tsunoda, Ikuo

7 ( 1 )  , p.10496 , 2017-09 , Nature Publishing Group
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.

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