Susceptibility of mice deficient in CD1D or TAP1 to infection with Mycobacterium tuberculosis.
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.
Behar
S M
SM
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. sbehar@rics.bwh.harvard.edu
Dascher
C C
CC
Grusby
M J
MJ
Wang
C R
CR
Brenner
M B
MB
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000276:immunology*; D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity*; D013234:Stem Cells / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology*; D001613:beta 2-Microglobulin / Q000235:genetics
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D001613:beta 2-Microglobulin