Protective immunity to influenza virus
CD4 T cells are a central component of protective immunity to influenza, acting both by potentiating responses of other lymphoid cells and by direct mediators of protective immunity. Our laboratory is committed to dissecting the elements in the CD4 T cell repertoire in humans that are predictors of protective immunity to influenza virus infections and future protective immune responses to vaccination. To address these issues, we probe the human CD4 T cell repertoire in order to quantify the CD4 T cell viral antigen specificity and phenotypic markers of CD4 T cells associated with the discreet functional subsets of CD4 T cells. Of particular interest in the human CD4 T cell repertoire are circulating follicular helper cells, cytokine secreting CD4 T cells and cytotoxic CD4 T cells. We use multiparameter flow cytometry, MHC-peptide tetramers and peptide specific EliSpot assays, to identify these key subsets of circulating influenza-specific CD4 T cells before and after vaccination by newly developed licensed vaccines or after natural infection with circulating influenza viruses.
We also use animal models of infection and vaccination to explore new strategies to foster protective immunity. We currently have projects related to novel vaccines to promote protective immunity to avian and potentially pandemic strains of influenza viruses as well as novel intranasal vaccines that are being explored for their utility in facilitating expansion and maintenance of lung tissue localized CD4 T cells or CD4 T cells that can be rapidly recalled after infection. Major tools for these studies include multiparameter flow cytometry to detect localization of virus-specific CD4 T cells in the respiratory tract and expression of markers associated with T cell homing or distinct effector functions. We have also developed influenza reporter viruses that allow us to directly detect infected and antigen bearing cells.
Because our work is highly interdisciplinary, we currently have exciting collaborations with virologists and infectious disease specialists inside the University and the larger influenza community nationally and internationally, providing a wide range of expertise and clinically relevant, research-focused training opportunities.