title: T lymphocytes mediating protection and cellular cytolysis during the course of Mycobacterium tuberculosis infection. Evidence for different kinetics and recognition of a wide spectrum of protein antigens.
abstract: Recent evidence suggests the existence of at least two pathways of acquired specific resistance to Mycobacterium tuberculosis infection; the first consisting of cytokine-mediated activation of parasitized host cells by protective T cells, and the second involving the lysis of these cells by cytolytic T cells. Evidence presented in this report shows that both of the above mechanisms are operative in experimentally infected mice, but that they differ markedly in terms of their kinetics of emergence and loss. It was found that protective T cell activity was acquired very early during the course of the infection, and was temporally associated with the onset of bacterial elimination; however, cytolytic activity did not peak until 10 to 20 days later. This report shows further that the target Ag of these effector T cell populations were apparently numerous with no evidence for preferential recognition of a few immunodominant Ag. In view of the preponderance of target proteins in the bacterial filtrate, we present the hypothesis that such proteins secreted or otherwise leaked from the dividing mycobacterium are pinocytosed from the phagosome and used by the infected macrophage as the key protective Ag leading to T cell sensitization. This hypothesis thus explains the preferential requirement for the viable bacterium in the generation of specific resistance, and further explains why protective immunity is generated even while the organism is still multiplying in an apparently unrestrained manner.
authors.affiliation: Department of Microbiology, Colorado State University, Fort Collins 80523.
authors.forename: I M
authors.initials: IM
authors.lastname: Orme
authors.forename: E S
authors.initials: ES
authors.lastname: Miller
authors.forename: A D
authors.initials: AD
authors.lastname: Roberts
authors.forename: S K
authors.initials: SK
authors.lastname: Furney
authors.forename: J P
authors.initials: JP
authors.lastname: Griffin
authors.forename: K M
authors.initials: KM
authors.lastname: Dobos
authors.forename: D
authors.initials: D
authors.lastname: Chi
authors.forename: B
authors.initials: B
authors.lastname: Rivoire
authors.forename: P J
authors.initials: PJ
authors.lastname: Brennan
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D003593:Cytoplasm / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006360:Heat-Shock Proteins / Q000276:immunology; D006825:Hybridomas; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000648:ultrastructure; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; D007371:Interferon-gamma