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- W4313382637 abstract "Abstract Reactivation of chronic Toxoplasma gondii (T. gondii) infection and toxoplasmic encephalitis is a major health concern in immune compromised people. Dysregulated T-cell responses are thought to promote chronic Toxoplasmosis. The non-T-cell factors that contribute to T cell dysregulation and chronic T. gondii infection are unclear. We have discovered that NKp46+ NK cells paradoxically increase the frequency and number of IFNγ+TNFα+CD4+ T-cells in the brain in during chronic T. gondii infection. Depletion of NK cells resulted in a decrease in polyfunctional brain CD4+ T-cells and an increase in IFNγ+Grzb+CD8+ T-cell responses in the brain. This decrease in CD4+ T-cell and increase in CD8+ T-cell responses correlated with better survival of chronically infected mice. This result suggests that NKp46+ NK cells drive an NK cell-dependent CD4+ T cell response that is detrimental to the CD8+ T cell response important for controlling chronic T. gondii infection. In support of this possibility, adoptive transfer of NK cell-dependent CD4+ T cells into chronically infected mice reduced polyfunctional CD8+ T-cell responses in the brain while CD4+ T cells generated in the absence of NK cells during chronic T. gondii infection did not. NKp46+ NK cells were not found in brain tissue, but appear to localize to the vasculature of the brain and periphery during chronic T. gondii infection. Surprisingly, we observe that NKp46+ NK cells increase their expression of MHC Class II. Our results lead us to hypothesize that during chronic T. gondii infection NKp46+ NK cells acquire the ability to prime CD4+ T-cell responses via MHC Class II expression resulting in decreased polyfunctional CD8 T cell responses to promote parasite persistence." @default.
- W4313382637 created "2023-01-06" @default.
- W4313382637 creator A5031976319 @default.
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- W4313382637 date "2019-05-01" @default.
- W4313382637 modified "2023-09-27" @default.
- W4313382637 title "NKp46+ NK cells regulate brain CD4+ T cells to promote chronic <i>Toxoplasma gondii</i> infection" @default.
- W4313382637 doi "https://doi.org/10.4049/jimmunol.202.supp.190.72" @default.
- W4313382637 hasPublicationYear "2019" @default.
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