Almost all children have been infected with RSV by the age of 2 years, some more than once. RSV infection is the most common event that precipitates wheezing in children and response to RSV in infancy strongly predicts the presence of childhood asthma. Thus, characterizing the T cell response to RSV may provide insight towards understanding childhood asthma. To that end, there are two experimental projects planned. The first is to define the T cell responses to RSV and other respiratory viruses by tonsil T cells. Tonsils are in an ideal anatomic location for RSV antigen presentation, and thus should contain an abundance of RSV specific cells. The studies will be done with cells in suspension, and with tonsil histocultures. Histocultures are an excellent model to study RSV specific responses because anatomic structure and cellular composition are intact. Furthermore, use of a GFP-expressing virus allows tracking of infected cells and the immune response to RSV. Clinical histories of the tonsil donors will allow correlation of immune responses with asthma. The second project addresses the need for immunological correlates of protection to viruses to which neutralizing antibodies are insufficient or irrelevant. In these cases (such as RSV and HIV) protection is dependent upon memory CD4 T cells, independent of their role as B cell helpers. It is not known, however, which subsets of memory CD4 T cells are best equipped for protection. Multiple memory cell subsets have been recently defined based on their expression of chemokine receptors and other homing receptors in combination with CD45 isoforms. The recent development of 10-12 parameter flow cytometry and cell sorting will allow subsets to be functionally defined and characterized, which in turn may be applied to clinical vaccine studies to determine correlates of protection. These results may be used to guide vaccine development in any case where cellular responses serve a critical role in protection.
