Follicular helper T cell and memory B cell immunity in CHC patients

Chronic hepatitis C (CHC) is associated with biological activity of T follicular helper (Tfh) cells and memory B cells (MBCs). However, the nature of Tfh cell subsets that are responsible for MBCs in CHC patients has not been evaluated. This study aimed to investigate Tfh and MBC immunity before and after direct-acting antiviral (DAA) therapy in patients with CHC. A total of 31 CHC patients and 15 healthy controls (HCs) were recruited. Individual patients were treated with sofosbuvir/ribavirin (SOF/RBV) or in combination with pegylated interferon alpha-2a (PEG-IFN-α-2a) for 12 weeks. Immunofluorescence revealed the frequency of ICOS⁺CD4⁺CXCR5⁺ active Tfh cells in liver tissue of CHC patients was higher than that of healthy control. Tfh and B cell co-culture experiments showed that Tfh2 cells from CHC patients have potential ability to induce B cell differentiation and IgG production. Flow cytometry showed that the frequencies of CD21^-CD27⁺IgD^- activated MBCs, ICOS⁺CD4⁺CXCR5⁺ activated Tfh cells, Tfh1 (IFN-γ⁺CD4⁺CXCR5⁺) cells, and Tfh2 (IL-4⁺CD4⁺CXCR5⁺) cells, but not of Tfh17 (IL-17⁺CD4⁺CXCR5⁺) cells, increased in CHC patients before and after DAA therapy. Collectively, ICOS⁺ Tfh, Tfh1, Tfh2 cells, and MBCs participated in the antiviral treatment process of SOF/RBV with or without PEG-IFN-α-2a in CHC patients, and their activity was further enhanced during the treatment. KEY MESSAGES: This study aimed to investigate Tfh cells and MBC immunity in CHC patients. CD21^-CD27⁺IgD^- activated MBCs increased in CHC patients before and after treatment. Tfh1 and Tfh2 cells increased in CHC patients before and after antiviral treatment. Intrahepatic activated Tfh cells increased in CHC patients before treatment. Tfh2 cells from CHC patients have a stronger ability to induce B cell differentiation.