Regulation of immunity during viral lung infection (168.1)

Abstract

Regulatory T cells (Tregs) play a clear role in chronic infections and inflammatory disorders, but their role in acute infections have not been fully elucidated. Respiratory syncytial virus (RSV) is the major cause of serious lower respiratory tract infection in infants, resulting in over-exuberant immune responses. In order to examine the role of Tregs in primary RSV primary infection, we infected “Depletion of regulatory T cells” (DEREG) mice which express the diphteria toxin (DT) receptor enhanced GFP fusion protein under the control of FOXP3 gene locus. Injections of DT ablated Tregs, and depletion prior to RSV primary infection caused increased weight loss and increased influx of cells into the lung and the airways (bronchioalveolar lavage, BAL) with lung and BAL showing elevated numbers of CD4+ and CD8+ T cells on d4, d8 and d14 post RSV infection. Interestingly, Treg depletion also caused an increase in neutrophils and eosinophils in the airways. Therefore, Tregs do not only control the magnitude of the T cell response, but also the quality of the responses that follow. The effects of RSV infection in mice with defective immune regulation closely parallels the observed effects of RSV in children with bronchiolitis, suggesting that the pathogenesis of bronchiolitis may involve an inability to regulate virus-induced inflammation