Examining the CD4 T cell response after RSV infection

The overall goal of my project is to fully characterize the CD4 T cell response against RSV. RSV is the most common cause of viral lower respiratory tract infections in infants and children and a major source of morbidity and mortality in the elderly and immunocompromised individuals. Previous efforts to create a RSV vaccine have been met with failure including vaccination with a formalin-inactivated RSV vaccine that caused exacerbated disease in children that subsequently contracted a natural RSV infection. CD4 T cells are required to mediate the development of RSV vaccine-enhanced disease. However, efforts to identify the effector mechanisms utilized by RSV-specific memory CD4 T cells to mediate the induction of RSV vaccine-enhanced disease are currently hampered by the lack of defined RSV-specific CD4 epitopes. Current technologies such as MHC Class II tetramers or intracellular cytokine staining (ICS) requires knowledge of the CD4 T cell epitopes in order to follow pathogen-specific CD4 T cell responses. Therefore, the goal of my project was to develop novel methodologies to identify antigen-specific CD4 T cells and then use these methodologies to study RSV-specific CD4 T cell responses.

McDermott DS, Knudson CJ, Varga SM. Determining the breadth of the respiratory syncytial virus-specific T cell response. J Virol. 2014 Mar;88(6):3135-43. doi:10.1128/JVI.02139-13. Epub 2013 Dec 26. PubMed PMID: 24371055; PubMed Central PMCID: PMC3957923.

Olson MR*, McDermott DS*, Varga SM. The initial draining lymph node primes the bulk of the CD8 T cell response and influences memory T cell trafficking after a systemic viral infection. PLoS Pathog. 2012;8(12):e1003054. doi:10.1371/journal.ppat.1003054. Epub 2012 Dec 6. PubMed PMID: 23236277; PubMed Central PMCID: PMC3516554. *co-first author.

McDermott DS, Varga SM. Quantifying antigen-specific CD4 T cells during a viral infection: CD4 T cell responses are larger than we think. J Immunol. 2011 Dec 1;187(11):5568-76. Epub 2011 Oct 31. PubMed PMID: 22043009; PubMed Central PMCID: PMC3221938

McDermott DS, Weiss KA, Knudson CJ, Varga SM. Central role of dendritic cells in shaping the adaptive immune response during respiratory syncytial virus infection. Future Virol. 2011 Aug;6(8):963-973. PubMed PMID: 21887154; PubMed Central PMCID: PMC3163480.