The CD4 T cell response to respiratory syncytial virus infection

• Published in: Immunologic research 2014-08, Vol.59 (1-3), p.109-117
• Main Authors: Christiaansen, Allison F., Knudson, Cory J., Weiss, Kayla A., Varga, Steven M.
• Format: Article
• Language: English
• Subjects: Allergology; Animal models; Animals; Babies; Biomedical and Life Sciences; Biomedicine; Bronchopneumonia; CD4 antigen; Cytokines; Cytokines - genetics; Cytokines - immunology; Female; Helper cells; Humans; Immune clearance; Immune response; Immune system; Immunization; Immunology; Immunology at the University of Iowa; Immunoregulation; Infant; Infants; Infections; Inflammation; Interleukin 10; Interleukin 13; Interleukin 17; Internal Medicine; Lymphocytes; Lymphocytes T; Male; Medicine/Public Health; Portraits as Topic; Regulation; Respiratory function; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - genetics; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - pathology; Respiratory Syncytial Virus Infections - prevention & control; Respiratory Syncytial Virus Vaccines - adverse effects; Respiratory Syncytial Virus Vaccines - immunology; Respiratory Syncytial Viruses - genetics; Respiratory Syncytial Viruses - immunology; Respiratory tract; Respiratory tract diseases; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - pathology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - pathology; Vaccination; Vaccines; Viruses
• ISSN: 0257-277X; 1559-0755
• DOI: 10.1007/s12026-014-8540-1

Respiratory syncytial virus (RSV) can induce severe lower respiratory tract infections in infants and is the leading cause of bronchiolitis in children worldwide. RSV-induced inflammation is believed to contribute substantially to the severity of disease. T helper (Th)2-, Th9-, and Th17-related cytokines are all observed in infants hospitalized following a severe RSV infection. These cytokines cause an influx of inflammatory cells, resulting in mucus production and reduced lung function. Consistent with the data from RSV-infected infants, CD4 T cell production of Interleukin (IL)-9, IL-13, and IL-17 has all been shown to contribute to RSV-induced disease in a murine model of RSV infection. Conversely, murine studies indicate that the combined actions of regulatory factors such as CD4 regulatory T cells and IL-10 inhibit the inflammatory cytokine response and limit RSV-induced disease. In support of this, IL-10 polymorphisms are associated with susceptibility to severe disease in infants. Insufficient regulation and excess inflammation not only impact disease following primary RSV infection it can also have a major impact following vaccination. Prior immunization with a formalin-inactivated (FI-RSV) vaccine resulted in enhanced disease in infants following a natural RSV infection. A Th2 CD4 T cell response has been implicated to be a major contributor in mediating vaccine-enhanced disease. Thus, future RSV vaccines must induce a balanced CD4 T cell response in order to facilitate viral clearance while inducing proper regulation of the immune response.