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- W4313408099 abstract "Abstract T cells that express TCF1 display self-renewing capacity and are essential for the long-term T cell response during chronic infections and cancer. Due to their increased responsiveness to checkpoint blockade, TCF1+ T cells are recognized as promising targets for immunotherapies. We found that, in contrast to T cells responding to infections (Tinf), the majority of adjuvanted subunit vaccine-elicited T cells (Tvac) rapidly acquired a memory phenotype (CD127hi) and were TCF1hi. This suggests that Tvacs could be programmed by TCF1 to commit to a memory cell fate. We found that Tvac peak and memory responses were more compromised in the absence of TCF1 than those of Tinf. However, TCF1 KO Tvacs still developed memory, suggesting that additional factors were involved. FOXO1 is important for T cell memory after infections. We found that Tvacs expressed more FOXO1 than Tinfs. In contrast to Tinf, FOXO1 was required for both the peak and memory Tvac responses. Moreover, even though FOXO1 drives TCF1 in Tinfs, Tvacs expressed TCF1 independently of FOXO1. To explore the cause for such high expression of TCF1 and FOXO1 in Tvacs, we next examined the role of inflammatory mediators in their regulation. Tvac TCF1 and FOXO1 inversely correlated with adjuvant-elicited pro-inflammatory signals. Moreover, addition of pro-inflammatory TLR9 ligand CpG reduced Tvac TCF1, FOXO1 and memory. In contrast to prior reports, anti-IL-12 failed to reverse the effect of CpG on Tvacs. Anti-IFNγ, however, restored the Tvac memory phenotype even as CpG drove additional inflammatory mediators. Our data highlight the differences in the transcriptional regulation of vaccine- and infection-elicited T cells and provide insights into the mechanisms regulating TCF1 and FOXO1. Supported by grants from NIH (T32 AI074491, R01 AI066121)" @default.
- W4313408099 created "2023-01-06" @default.
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- W4313408099 date "2022-05-01" @default.
- W4313408099 modified "2023-09-26" @default.
- W4313408099 title "Inflammation suppresses elevated TCF1 and FOXO1 expression in vaccine-elicited T cells" @default.
- W4313408099 doi "https://doi.org/10.4049/jimmunol.208.supp.122.28" @default.
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