Dysfunction of circulating follicular helper T cells in people living with HIV who are HBV small surface protein antibody (HBsAb)-negative despite HBV vaccination

Background The seroconversion rate after hepatitis B virus (HBV) vaccination in people living with human immunodeficiency virus (HIV) is reportedly lower than that in non-HIV controls. Follicular helper T (Tfh) cells play a central role in humoral immunity, and IL-21 secreted by Tfh cells is essential for B cells to differentiate into plasma cells. This study investigated the frequency and function of circulating Tfh (cTfh) cells isolated from people living with HIV (PWH) who are negative for hepatitis B virus (HBV) surface antigen (HBsAb−) in a small cohort of PWH who received HBV vaccination. Case presentation The frequency of cTfh cells in HBsAb− PWH (HBsAb levels less than 10 mIU/mL) was the same as that in non-HIV controls and HBsAb positive (HBsAb+) PWH, who maintained HBsAb at 10 mIU/mL for at least 1 year after receiving three doses of the HBV vaccine. However, after immune stimulation with anti-CD3/CD28 antibodies, the frequency of cTfh cells in the non-HIV controls and HBsAb+ PWH increased, whereas the frequency of cTfh cells in the HBsAb− PWH tended to be more gradual. cTfh17-like and cTfh2-like cells, subsets of cTfh cells, are involved in humoral immunity, and PD-1 regulates the function of these cells in the germinal center. The frequencies of PD-1+ cTfh17-like and cTfh2-like cells at baseline did not differ significantly among the three groups. However, HBsAb− PWH had a lower frequency of PD-1+ cTfh17-like cells after immune stimulation than non-HIV controls did. The frequencies of PD-1+ cTfh17-like cells and cTfh2-like cells with high PD-1 expression were significantly lower in HBsAb− PWH than in non-HIV controls. Furthermore, the production of IL-21, which is essential for plasma cell differentiation, tended to be lower in HBsAb− PWH than in non-HIV controls or HBsAb+ PWH. Conclusions cTfh cells isolated from HBsAb− PWH may be unable to produce sufficient IL-21 after immune stimulation. This study is the first to suggest that cTfh cells may not function adequately in some PWH. This study highlights the need for large-scale validation of cTfh cell frequency and function in PWH. Clinical trial number Not applicable.