Enhanced IL-2 in early life limits the development of T(FH) and protective antiviral immunity

T follicular helper cell (T(FH))–dependent antibody responses are critical for long-term immunity. Antibody responses are diminished in early life, limiting long-term protective immunity and allowing prolonged or recurrent infection, which may be important for viral lung infections that are highly prevalent in infancy. In a murine model using respiratory syncytial virus (RSV), we show that T(FH) and the high-affinity antibody production they promote are vital for preventing disease on RSV reinfection. Following a secondary RSV infection, T(FH)-deficient mice had significantly exacerbated disease characterized by delayed viral clearance, increased weight loss, and immunopathology. T(FH) generation in early life was compromised by heightened IL-2 and STAT5 signaling in differentiating naive T cells. Neutralization of IL-2 during early-life RSV infection resulted in a T(FH)-dependent increase in antibody-mediated immunity and was sufficient to limit disease severity upon reinfection. These data demonstrate the importance of T(FH) in protection against recurrent RSV infection and highlight a mechanism by which this is suppressed in early life.