Protective role of γ/δ T cells and α/β T cells in tuberculosis

Abstract

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