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Enhanced IL-2 in early life limits the development of TFH and protective antiviral immunity

2021 Pyle et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). https://creativecommons.org/licenses/by/4.0 ;ISSN: 0022-1007 ;EISSN: 1540-9538 ;DOI: 10.1084/jem.20201555

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  • Title:
    Enhanced IL-2 in early life limits the development of TFH and protective antiviral immunity
  • Author: Pyle, CJ ; Labeur-Iurman, L ; Groves, HT ; Puttur, F ; Lloyd, CM ; Tregoning, JS ; Harker, JA
  • Subjects: 11 Medical and Health Sciences ; Immunology
  • Description: 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.
  • Publisher: Rockefeller University Press
  • Creation Date: 2021-09
  • Language: English
  • Identifier: ISSN: 0022-1007
    EISSN: 1540-9538
    DOI: 10.1084/jem.20201555
  • Source: Spiral
    GFMER Free Medical Journals
    PubMed Central
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