| First Author | Pyle CJ | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 12 | PubMed ID | 34665220 |
| Mgi Jnum | J:312858 | Mgi Id | MGI:6794024 |
| Doi | 10.1084/jem.20201555 | Citation | Pyle CJ, et al. (2021) Enhanced IL-2 in early life limits the development of TFH and protective antiviral immunity. J Exp Med 218(12) |
| abstractText | T follicular helper cell (TFH)-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 TFH and the high-affinity antibody production they promote are vital for preventing disease on RSV reinfection. Following a secondary RSV infection, TFH-deficient mice had significantly exacerbated disease characterized by delayed viral clearance, increased weight loss, and immunopathology. TFH 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 TFH-dependent increase in antibody-mediated immunity and was sufficient to limit disease severity upon reinfection. These data demonstrate the importance of TFH in protection against recurrent RSV infection and highlight a mechanism by which this is suppressed in early life. |
