Figure 4: Survival of TAP1−/− CD1−/− mice infected with M. tuberculosis. CD1D−/−TAP1−/− or CD1D+TAP1−/− littermate controls were infected with 106 M. tuberculosis. There were no statistically significant differences in survival (P = 0.95).

Mentions: To exclude the possibility of a subtle CD1d-dependent effect that was obscured in the presence of CD8+ T cells, the survival of TAP1−/−CD1D−/− mice was compared with TAP1−/−CD1D+/+ mice, on a mixed 129/Sv and C57BL/6 genetic background. No significant difference was observed in the survival of these strains of mice (Fig. 4). The MST was 79 d for the TAP1−/−CD1D−/− mice and 65 d for the TAP1−/−CD1D+/+ mice, which was similar to other experiments in which TAP1−/−CD1D+/+ mice were infected (Fig. 3). This experiment is consistent with the conclusion that CD1d does not contribute to a protective immune response after intravenous inoculation with M. tuberculosis.

Behar SM, Dascher CC, Grusby MJ, Wang CR, Brenner MB - J. Exp. Med. (1999)

Bottom Line: Here, we delineate the contribution of class I MHC-restricted T cells in the defense against tuberculosis as transporter associated with antigen processing (TAP)1-deficient mice died rapidly, bore a greater bacterial burden, and had more severe tissue pathology than control mice.In contrast, CD1D-/- mice were not significantly different in their susceptibility to infection than control mice.This data demonstrates a critical role for TAP-dependent peptide antigen presentation and provides further evidence that class I MHC-restricted CD8(+) T cells, the major T cell subset activated by this antigen processing pathway, play an essential role in immunity to tuberculosis.

Affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. sbehar@rics.bwh.harvard.edu

Abstract: Cellular immunity against Mycobacterium tuberculosis controls infection in the majority of infected humans. Studies in mice have delineated an important role for CD4(+) T cells and cytokines including interferon gamma and tumor necrosis factor alpha in the response to infection with mycobacteria. Recently, the identification of CD8(+) CD1-restricted T cells that kill M. tuberculosis organisms via granulysin and the rapid death after infection of beta2 microglobulin deficient mice in humans has drawn attention to a critical role for CD8(+) T cells. The nature of mycobacterial-specific CD8(+) T cells has been an enigma because few have been identified in any species. Here, we delineate the contribution of class I MHC-restricted T cells in the defense against tuberculosis as transporter associated with antigen processing (TAP)1-deficient mice died rapidly, bore a greater bacterial burden, and had more severe tissue pathology than control mice. In contrast, CD1D-/- mice were not significantly different in their susceptibility to infection than control mice. This data demonstrates a critical role for TAP-dependent peptide antigen presentation and provides further evidence that class I MHC-restricted CD8(+) T cells, the major T cell subset activated by this antigen processing pathway, play an essential role in immunity to tuberculosis.