Frequency of gC1qRCD4 T cells increases during acute hepatitis C virus infection and remains elevated in patients with chronic infection

CD4⁺ T cell responses are impaired in chronic HCV infection. To determine factor(s) involved in CD4⁺ T cell dysregulation, we examined the effect of extracellular core on the alteration of CD4⁺ T cell responses and the cell surface level of core-binding protein, gC1qR on CD4⁺ T cells from acute HCV patients with resolved and chronic infection. During the acute phase of infection, the frequency of gC1qR⁺CD4⁺ T cells increased in both resolved and chronic HCV infection compared to healthy controls. Notably, 6 months later, the frequency of gC1qR⁺CD4⁺ T cells maintained elevated in chronic patients compared to that in resolved patients. In addition, TCR stimulation increased the frequency of gC1qR⁺CD4⁺ T cells, resulting in core-induced inhibition of T cell responses in both resolved and chronic patients. These results suggest that HCV infection expands gC1qR⁺CD4⁺ T cells, which increase the susceptibility to core-mediated immune dysregulation and facilitate the establishment of HCV persistency.