The CD4 T cell response to respiratory syncytial virus infection.
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.
Department of Microbiology, University of Iowa, 51 Newton Road, 3-532 BSB, Iowa City, IA, 52242, USA.
Allison F
AF
Christiaansen
Cory J
CJ
Knudson
Kayla A
KA
Weiss
Steven M
SM
Varga
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011173:Portraits as Topic; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D022261:Respiratory Syncytial Virus Vaccines / Q000009:adverse effects / Q000276:immunology; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D014611:Vaccination
D016207:Cytokines; D022261:Respiratory Syncytial Virus Vaccines