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Transcriptional profiling of CD4+ T cells with high, intermediate and low PD-1 and ICOS co-expression from HCV infected chimpanzees

ABSTRACT: A sustained CD4+ T cell response is required for resolution of acute HCV infection but remains poorly characterized. Here, CD4+ T cells with high PD-1 and ICOS co-expression expanded in the blood of chimpanzees during acute HCV infection. The peak response was comprised primarily of HCV-specific populations and temporally associated with acute hepatitis, seroconversion, and initial control of HCV replication. Circulating PD-1hiICOShi CD4+ T cells differentially expressed genes associated with Tfh, Th1, and cytotoxic signatures. Co-production of Tfh (CXCL13, IL-21) and Th1 (IFN-) effector molecules was observed after HCV antigen stimulation. HCV-specific Tfh1 CD4+ T cells infiltrated liver, consistent with expression of chemokine receptors that mediate homing to inflamed tissues. Most were CXCR5-negative and therefore resembled Tph/Tfhx13 CD4+ T cells recently described in cancer and autoimmune conditions. Detailed transcriptional, phenotypic, and functional analysis of the protective CD4+ T cell response presented here is expected to aid HCV vaccine development.

ORGANISM(S): Pan troglodytes

PROVIDER: GSE247812 | GEO | 2024/11/14

REPOSITORIES: GEO

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