title: Cytotoxic T lymphocytes in resistance to tuberculosis.
abstract: Recent experimental evidence has suggested T cells recognizing antigens in the context of both classical MHC class I and nonclassical class I-like molecules contribute to protective responses against Mycobacterium tuberculosis (MTB) infection. Our aims were to characterize both types of T cells, and to explore the basis of communication between the tubercle bacilli and the MHC class I pathway of the host macrophage. A model system was developed using exogenously added ovalbumin as a surrogate antigen to study presentation by MTB-infected macrophages. Viable, virulent MTB and closely related mycobacterial species facilitated the presentation of ovalbumin on MHC class I molecules to CD8+ cytolytic T cells that was dependent upon the cytosolic transport of peptides, implying communication between the MTB phagosome and the host cell cytoplasm. MHC class I presentation of soluble antigens was mimicked by Listeria monocytogenes, which grows within the host cell cytoplasm, as well as its purified hemolysin. We have also characterized T cells that recognize nonpeptide MTB antigens presented by CD1 molecules. CD1-restricted T cells demonstrated to lyse macrophages infected with virulent MTB were divided into distinct subsets based on surface phenotype (CD4-CD8- versus CD8-) and cytotoxicity mechanism (Fas receptor-mediated versus granule exocytosis). A functional consequence of these two mechanisms was observed that while both subsets lysed infected macrophages, only those T cells utilizing the granule exocytosis pathway were able to reduce viability of intracellular MTB.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Mazzaccaro
authors.forename: S
authors.initials: S
authors.lastname: Stenger
authors.forename: K L
authors.initials: KL
authors.lastname: Rock
authors.forename: S A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: M B
authors.initials: MB
authors.lastname: Brenner
authors.forename: R L
authors.initials: RL
authors.lastname: Modlin
authors.forename: B R
authors.initials: BR
authors.lastname: Bloom
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology*; D009161:Mycobacterium / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial