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- W4313373469 abstract "Abstract In response to viral infection, antigen-specific CD4 T cells differentiate into Th1 and T follicular helper (Tfh) cell subsets that acquire distinct DNA demethylation changes which act to enforce their lineage commitment and functions. Following viral clearance, the populations of Th1 and Tfh cells contract and form distinct memory populations that maintain their specific methylation programming. Previously, we found that deficiency of Tet2, an oxygenase that mediates CpG demethylation, skews the balance of Th1 and Tfh cells at 7 days post infection leading to the formation of significantly more germinal center (GC) Tfh cells. Here we examined whether Tet2 impacts CD4 T cell memory formation and the recall of lineage specific functions upon re-challenge. At days 15, 30, and 45 post infection with lymphocytic choriomeningitis virus (LCMV) there was a greater frequency of Tet2 deficient cells positive for memory markers in the blood when compared to WT cells. To assess the recall ability of Tet2 deficient memory CD4 T cells, Tet2KO and WT memory cells were purified from spleens of recipient mice at 90 days post-infection and equivalent numbers of WT and Tet2KO cells were then re-transferred into naive C57BL6/J recipient mice followed by LCMV infection. At 7 days post re-challenge, we observed a greater secondary expansion of Tet2KO cells compared to WT. Tet2KO memory cells also retained the ability to generate higher frequencies of GC Tfh cells in response to re-challenge. Ongoing work will identify whether Tet2 deficient memory Tfh cells can provide enhanced help for B cells during secondary infection and improve the antibody response. Taken together, these data suggest that Tet2 can act to restrict memory differentiation in CD4 T cells." @default.
- W4313373469 created "2023-01-06" @default.
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- W4313373469 date "2020-05-01" @default.
- W4313373469 modified "2023-10-17" @default.
- W4313373469 title "Deficiency of the methylcytosine dioxygenase Tet2 enhances CD4 T cell memory generation" @default.
- W4313373469 doi "https://doi.org/10.4049/jimmunol.204.supp.81.14" @default.
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