CXCR5+PD-1+CD8+ T cells are a novel T helper cell sublineage and are negatively regulated by Stat5 [scRNA-Seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE136641 | GEO | 2019/08/30
REPOSITORIES: GEO
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Project description:Effective immunity to viruses such as influenza and SARS-CoV-2 requires the generation of CD4+ T cell subsets that coordinate complementary aspects of the immune response. These include T follicular helper (TFH) and T helper 1 (TH1) cells, which promote humoral and cell-mediated helper responses, respectively. A third population, CD4+ cytotoxic T lymphocytes (CD4-CTLs) facilitates clearance of infection via mechanisms normally associated with CD8+ T cells, including perforin-mediated destruction of infected cells. Here, we identify the transcription factor Aiolos as a reciprocal regulator of TFH and CD4-CTL responses. We demonstrate that Aiolos deficiency compromises TFH differentiation and antibody production during influenza infection. Conversely, we find that CD4+ T cells acquire a cytotoxic-like program in the absence of Aiolos, including increased expression of the CTL-associated transcription factors Eomes and Blimp-1. We further show that while Aiolos positively regulates the TFH transcriptional regulators Zfp831, Tcf-1 and Bcl-6, it also directly represses expression of IL-2Ra and IL-2/STAT5-driven expression of the cytotoxic gene program. Thus, our findings identify Aiolos as a pivotal regulator of TFH and CD4-CTL differentiation and highlight its potential as a therapeutic target for the manipulation of CD4+ T cell humoral and cytotoxic responses.
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