The Acquired Immune Response to M. Tuberculosis

M. tuberculosis remains one of the most successful human pathogens. The ability of M. tuberculosis to elicit vigorous acquired immune responses and use of the macrophage as primary cell to infect, suggest that the organism has evolved multiple strategies to survive and persist in the face of innate and acquired immune responses. Persistence of M. tuberculosis in otherwise healthy persons is one of the hallmarks of this organism. Survival and persistence require not only resistance to microbicidal mechanisms of phagocytes but also avoidance of recognition by multiple T cell subsets. The acquired immune response to M. tuberculosis requires participation by multiple T cells subsets. These include not only a central role for MHC-II restricted CD4+ T cells, but also MHC-1 restricted CD8+, gamma-delta and CD-1 restricted T cells. These diverse T cell populations recognize a wide range of mycobacterial antigens, but share overlapping functions such as secretion of IFN-γ and TNF-α, CTL function, and ability to provide cell-contact dependent help to macrophages. How T cell responses are regulated in vivo and their roles in different stages of 104 M. tuberculosis infection and in protective immunity remain to be determined. Answers to these questions will impact vaccine development as well as understanding the host-pathogen interaction in M. tuberculosis infection.