title: Susceptibility of mice deficient in CD1D or TAP1 to infection with Mycobacterium tuberculosis.
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.
authors.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
authors.forename: S M
authors.initials: SM
authors.lastname: Behar
authors.forename: C C
authors.initials: CC
authors.lastname: Dascher
authors.forename: M J
authors.initials: MJ
authors.lastname: Grusby
authors.forename: C R
authors.initials: CR
authors.lastname: Wang
authors.forename: M B
authors.initials: MB
authors.lastname: Brenner
mesh_terms: 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
chemical_list: 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