PROTECTIVE ROLE OF GAMMA/DELTA T-CELLS AND ALPHA/BETA T-CELLS IN TUBERCULOSIS

Tuberculosis is a chronic infectious disease which causes major health problems globally. Although acquired resistance crucially depends on alpha/beta lymphocytes, circumstantial evidence suggests that, in addition, gamma/delta T lymphocytes contribute to protection against tuberculosis. We have studied Mycobacterium tuberculosis infection in TcR-delta(-/-) or TcR-beta(-/-) gene deletion mutants which completely lack gamma/delta T cells or alpha/beta T cells, respectively. Low inocula of M. tuberculosis led to death of TcR-beta(-/-) mice and transient disease exacerbation in TcR-delta(-/-) mutants. Infection with higher inocula caused rapid death of TcR-delta(-/-) mice. The development of and bacterial containment in granulomatous lesions was markedly impaired in TcR-beta(-/-), and less severly affected in TcR-delta(-/-) mutants. Mycobacteria-induced IFN-gamma production by spleen cells in vitro was almost abolished in TcR-beta(-/-) and virtually unaffected in TcR-delta(-/-) mice. Our data confirm the crucial role of alpha/beta T cells in protection against established tuberculosis and formally prove a protective role of gamma/delta T cells in early tuberculosis.