The focus of this proposal is to examine the significance of TH cells in RSV infection. this well recognized pathogen of infancy, is also responsible for severe respiratory disease in the elderly and the immunocompromised. Successful control of RSV has been hampered by an incomplete understanding of immunity to this virus. The contribution of TH cells in this response has not been well characterized. Initially the course of a primary RSV infection in mice deficient in CD4+ or CD8+ T cells will be studied. Duration of viral shedding, extent of lung pathology and effect on antibody production will be analyzed. To determine the role of TH cells in the maintenance of protection, RSV- immune mice will be depleted of T cell subsets and rechallenged with virus. The TH response to RSV, its proteins and its protective peptides will also be studied. The patterns of cytokine secretion will be examined for characteristics of TH1 or TH2 cells. TH1 cells, which secrete interleukin 2 (IL-1), interferon-gamma, and lymphotoxin, mediate delayed-type hypersensitivity reactions and cytotoxic functions. TH2 cells, which provide help for antibody synthesis and are thought to be important in allergic responses, secrete IL-4, IL-5, IL-6, and IL-10. A predominant TH1 or TH2 response may be a crucial determinant of an effective or detrimental reaction to this virus. Variations in the TH cell response to different forms of RSV antigen will be analyzed in spleen, lung and mediastinal lymph node cells. TH cell lines and clones will be developed and their effect in vivo examined. If data generated during the course of these experiments suggest a dominant role for CTL in RSV infection then the studies will be modified to include further analysis of CTL. Because of the myriad of interactions in which TH cells are involved, a better comprehension of TH cell activity should also enhance our overall understanding of immunity to RSV. This information will help overcome some of the current obstacles to successful prevention and treatment of RSV.
