Research SummaryIntermediate Fellowship research summary
CD4+ T lymphocytes are required to control Mycobacterium tuberculosis infection, yet despite high numbers of Mtb-specific CD4+ cells in infected individuals these cells do not eradicate this pathogen and nearly one thirdof the global population is infected. The TB vaccine, BCG is ineffective at preventing the most common form of the disease (pulmonary TB) and even more alarming, it is likely that there is no natural acquired immunity to Mtb (primary Mtbinfection does not prevent a secondary Mtb infection). What this latter point means is that a novel TB vaccine needs to be better than nature. One major barrier in developing better vaccines is our failure to understand the basic biology of CD4+ T cell mediated defense to this pathogen. My lab studies two major questions regarding the immune response to Mtb. First, what are the cellular and molecular mechanisms required for CD4-dependent defense? Second, how do we harness vaccine-induced CD4 effector cells to generate a rapid and sustained response following pulmonary infection? To address these questions, state of the art immunologic tools including MHC tetramers, and T cell receptor transgenic mice will be used to monitor the function of Mtb-specific CD4+ cells following aerosol infection of mice.