Enhanced IL-2 in early life limits the development of TFH and protective antiviral immunity
| Autor: | Clare M. Lloyd, Franz Puttur, John S. Tregoning, Chloe J. Pyle, James A. Harker, Helen T. Groves, Lucia Labeur-Iurman |
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| Přispěvatelé: | Wellcome Trust, Asthma UK, National Heart & Lung Institute Foundation |
| Rok vydání: | 2020 |
| Předmět: |
Interleukin 2
T Follicular Helper Cells Cell Immunology B-Lymphocyte Subsets Disease Respiratory Syncytial Virus Infections Antibodies Viral Virus Article Infectious Disease and Host Defense Interferon-gamma Immunity Pregnancy Immunopathology STAT5 Transcription Factor Immunology and Allergy Medicine Animals STAT5 11 Medical and Health Sciences Mice Inbred BALB C biology business.industry Age Factors Mucosal Immunology Germinal Center Mice Mutant Strains Immunity Humoral Mice Inbred C57BL medicine.anatomical_structure Reinfection biology.protein Proto-Oncogene Proteins c-bcl-6 Interleukin-2 Female Antibody business medicine.drug |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 |
| Popis: | Antibodies are central to long-term protection after infection or vaccination but often compromised in infancy. This study identifies a mechanism by which this compromise occurs and shows how it can be targeted to boost antibodies in early life and provide protection from reinfection. 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. |
| Databáze: | OpenAIRE |
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