Cytotoxic CD4+ T cells in Respiratory Syncytial Virus

This project will explore the role of CD4+ cytotoxic lymphocytes (CD4-CTL) during Respiratory syncytial virus (RSV) infection. Despite being a key cause of infant mortality, a major pathogen in the elderly and associated with COPD decline, there is still a great deal unknown about the immune response to this virus. Natural immunity does not develop in response to exposure and there is a marked association with CD4+ T cells and Th2 biased immune response in disease progression. In addition, CD4+ T cells are known to mediate MHC class II-restricted cytotoxicity which may be crucial to viral clearance, especially when the CD8+ T cell response is impaired as seen in several viral infections including RSV. While there is a growing body of evidence supporting the role of CD4-CTL in viral infections, relatively little is known about their activity in RSV. To investigate this, an ex vivo model of human lung infection will be used in conjunction with flow cytometry, IHC, ELISA and RT-qPCR with a view to demonstrating whether CD4-CTL are present and active in response to RSV infection and whether their activity has an effect on the surrounding tissue. As tissue availability will be a limiting factor, in vitro models of infection may also be used in which 2D and/or 3D cultures of RSV target cells can be analysed.