T cells play a critical role in the immune response to the intracellular pathogen M. tuberculosis, which is estimated to infect one third of the world's population. T cells regulate the acquired immune response which controls primary infection and provide protection against exogenous reinfection. CD4+ T cells traditionally have been considered the main T cell subset responsible for regulating protective immune responses to M. tuberculosis. However, in addition to the CD4+ T cell, both gamma-delta T cell receptor bearing T cells (gamma delta cells) and CD8+ T cells have a role in protective immunity to M. tuberculosis. The study of CD4+, CD8+ and gamma delta T cell responses to M. tuberculosis is the main interest of my laboratory.
The focus is on characterization of mycobacterial antigens recognized by CD4+ and gamma-delta T cells, the role of cytokines such as IL-2, IL-12, IFN-gamma, IL-10 and TGF-beta in modulating the T cell responses to M. tuberculosis, the functional interaction of antigen-specific T cells with macrophages infected with mycobacteria, and the mechanisms used by M. tuberculosis infected macrophages to process and present antigens from the phagosome to the cell surface to these different T cell subsets. Recent studies have focused on identifying molecules of M. tuberculosis that interfere with MHC-II antigen processing. Specifically the role of mycobacterial lipoproteins and TLR receptors in regulating MHC-II antigen processing has become a major focus.
These studies use cellular immunological and cell biologic approaches to study the biology of M. tuberculosis infected macrophages and T cells. In addition, a murine in vivo model of M. tuberculosis infection of the lung is used to study the unique micro-environment where M. tuberculosis infection occurs and immune responses are initiated.