Transcriptional profiling of CD4+ T cells with high, intermediate and low PD-1 and ICOS co-expression from HCV infected chimpanzees
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. Overall design: CD4+ T cells from HCV infected chimpanzees were sorted into 3 sub-populations PD-1/ICOS low (n=4), PD-1/ICOS intermediate (n=4) and PD-1/ICOS high (n=5) and transcriptional profililng was performed