biostudies-literatureBlasczyk HNIAID NIH HHSNational Institutes of HealthCanadian Institutes of Health Researche178089https://www.ebi.ac.uk/biostudies/studies/S-EPMC12578392biostudies-literatureUnknown135(21)Sustained CD4+ T cell immunity is required for resolution of acute hepatitis C virus (HCV) infection, but the response remains poorly characterized. Here, circulating CD4+ T cells with high programmed cell death 1 (PD-1) and ICOS coexpression were temporally associated with onset of virus control, seroconversion, and hepatitis in HCV-infected chimpanzees. Coproduction of T follicular helper (Tfh) (IL-21 and CXCL13) and Th1 (IFN-γ and TNF) cytokines after stimulation with HCV nonstructural proteins demonstrated that the response was predominately Tfh1 like and virus specific. Transcriptional analysis verified a Tfh1 lineage assignment. Effector-related genes such as ADGRG1 (GPR56), ZNF683 (Hobit), and KLRB1 (CD161) were also expressed. HCV-specific PD-1hiICOShi CD4+ Tfh1-like cells were enrThe Journal of clinical investigationA liver-infiltrating CD4+ Tfh1 cell response predicts HCV control, hepatitis, and seroconversion during acute infection.PMC12578392U01AI131313R01 AI126890U19AI159819R01AI136533U19 AI159819PJT-173467U01 AI131313R01 AI136533R01AI190069R01AI126890R01 AI190069Blasczyk HBremer WPhelps CCSkinner NBowen DGLanford RGrakoui AWalker CMZhou YXu ZShoukry NHfalseA liver-infiltrating CD4+ Tfh1 cell response predicts HCV control, hepatitis, and seroconversion during acute infection.Sustained CD4+ T cell immunity is required for resolution of acute hepatitis C virus (HCV) infection, but the response remains poorly characterized. Here, circulating CD4+ T cells with high programmed cell death 1 (PD-1) and ICOS coexpression were temporally associated with onset of virus control, seroconversion, and hepatitis in HCV-infected chimpanzees. Coproduction of T follicular helper (Tfh) (IL-21 and CXCL13) and Th1 (IFN-γ and TNF) cytokines after stimulation with HCV nonstructural proteins demonstrated that the response was predominately Tfh1 like and virus specific. Transcriptional analysis verified a Tfh1 lineage assignment. Effector-related genes such as ADGRG1 (GPR56), ZNF683 (Hobit), and KLRB1 (CD161) were also expressed. HCV-specific PD-1hiICOShi CD4+ Tfh1-like cells were enr2025-01-01T00:00:00Z2025 Nov2026-06-05T07:18:38.855Z2026-05-14T03:08:47.406ZS-EPMC125783924095661910.1172/JCI178089