This article investigates the characteristics and longevity of germinal center T follicular helper (GC-Tfh) cells in non-human primates immunized with an HIV Env protein vaccine. The authors show that an escalating-dose (ED) immunization regimen elicited stronger and more durable GC-Tfh cell responses, which significantly correlated with higher-quality neutralizing antibody titers. Using single-cell RNA sequencing, the study identifies several functionally distinct GC-Tfh subsets, such as IL-4hi and IL-21hi cells, and demonstrates that antigen-specific Tfh clones can persist for over six months without showing signs of exhaustion. Furthermore, the findings reveal that Tfh clones exhibit clonal migration between distal lymph nodes, highlighting a dynamic and widespread immune response critical for sustained humoral immunity.

References:

• Marina-Zárate E, Sutton H J, Lopez P G, et al. Highly functional and prolonged germinal center T follicular helper cell responses are associated with enhanced neutralizing antibody development[J]. Immunity, 2025.