Protective neutralizing influenza antibody response in the absence of T follicular helper cells

Virus infection induces the development of T follicular helper (T_FH) and T helper 1 (T_H1) cells. Although T_FH cells are important in anti-viral humoral immunity, the contribution of T_H1 cells to a protective antibody response remains unknown. We found that IgG2 antibodies predominated in the response to vaccination with inactivated influenza A virus (IAV) and were responsible for protective immunity to lethal challenge with pathogenic H5N1 and pandemic H1N1 IAV strains, even in mice that lacked T_FH cells and germinal centers. The cytokines interleukin-21 and interferon-γ, which are secreted from T_H1 cells, were essential for the observed greater persistence and higher titers of IgG2 protective antibodies. Our results suggest that T_H1 induction could be a promising strategy for producing effective neutralizing antibodies against emerging influenza viruses.