The role of T-cell subsets in Mycobacterium tuberculosis infection.

During the last 10 years, studies of the immune response to M. tuberculosis in humans and animal models have increased our understanding of the complex roles of T-cell subsets in protection against tuberculosis. Although CD4+ T cells remain the dominant and critical T-cell subset, others, such as gamma delta and CD8+ T cells, probably have important complementary roles. Since all three subsets are sources of IFN-gamma and competent cytotoxic effector cells, in vivo kinetics and differences in antigen processing/recognition likely will define how each T-cell subset functions in different phases of the immune response to M. tuberculosis. In addition, individuals may differ in terms of the dominance of CD8+ and gamma delta T cells as accessory T-cell populations. In some, gamma delta T cells; in others, CD8+ T cells; or both T-cell subsets may complement CD4+ T-cell function. Future studies in animal models (with human cells obtained from sites of infection such as lung or lymph node), characterizations of the antigen repertoire, and longitudinal immunoepidemiological studies should define more clearly how different T-cell subsets contribute to protection against M. tuberculosis. Such studies may determine how failure of T-cell subset function results in reactivation or progressive primary tuberculosis. Enhanced understanding of the function of, and antigen recognition by, T-cell subsets in M. tuberculosis infection also is necessary for the development of improved diagnostic tests and vaccines for tuberculosis.