Immunity to Tuberculosis. It is estimated that 1/3 of the world’s population has been infected with Mycobacterium tuberculosis (Mtb). In the majority of infected people, the immune response is able to adequately control the infection, and consequently only 5-10% will develop clinical disease during their lifetime. My long-term goal is to understand the immunological basis for protective immunity. One way we are investigating this problem is to determine why different mouse strains differ in their susceptibility to tuberculosis. We have observed that certain susceptible mouse strains are unable to efficiently recruit T cells to the lung following infection with Mtb, and this failure likely contributes to increased mortality and morbidity of susceptible mice. Therefore, we are particularly interested in the early events leading to the initiation of the pulmonary immune response following respiratory Mtb infection. This includes establishing how T cells and myeloid cells are recruited back to the lung and how these cells mediate their effector functions.

Although BCG is used universally as a vaccine, its efficacy in preventing pulmonary tuberculosis is controversial. Most Mtb infected individuals develop long-lived immunity that contains the infection in a T cell-dependent manner. Thus, there is considerable interest in how different T cell subsets contribute to immunity and whether vaccination can stimulate protective T cells. Delineating the role of CD8+ T cells in host immunity to Mtb has been hindered by the paucity of antigens known to be recognized by CD8+ T cells. Our antigen discovery program has successfully identified and defined several mycobacterial peptide epitopes that are recognized by CD8+ T cells. For example, CD8+ T cells specific for culture filtrate protein-10 (CFP10) are found in infected people, indicating that CFP10 can prime CD8+ T cells after infection. Notably, CFP10 is encoded in the RD1 genetic locus, which is associated with Mtb virulence. The aim of our studies is to identify, enumerate and functionally characterize antigen-specific CD8+ T cells that are elicited following pulmonary infection. Finally, we are determining whether these antigens can be used as vaccines to elicit protective immunity.