title: Anergy, IFN-gamma production, and apoptosis in terminal infection of mice with Mycobacterium avium.
abstract: We have followed the course of experimental infection of mice with Mycobacterium avium over an extended period, assessing bacterial numbers and T cell responsiveness. When mice were infected intranasally, bacteria spread to the spleen and liver, but remained in highest numbers in the lungs. Both CD4+ and CD8+ T cells, assayed at any time from 6-28 wk after infection, produced IFN-gamma. After initial rapid growth, bacterial numbers slowly increased from approximately 107 at 6 wk to more than 5 x 108 at 28 wk, indicating that the resistance mechanisms so generated were not adequate to contain the infection. During infection, apoptosis of both CD4+ and CD8+ T cells, measured immediately ex vivo by staining with Annexin V, increased steadily. With some individual exceptions, there was a close correlation between apoptosis of CD4+ cells and level of IFN-gamma production by cultured spleen cells. By 34 wk postinfection, there was an abrupt cessation of IFN-gamma production. No IL-4 was detected, ruling out a switch to Th2 profile. Subsequently, bacterial numbers increased still further to >5 x 109 per lung, and the mice lost body weight and would have died if not killed for experimental or humane reasons. The possibility that T cells exposed over this prolonged period to extremely high doses of Ag may become tolerant by a process of terminal differentiation is discussed.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Gilbertson
authors.forename: J
authors.initials: J
authors.lastname: Zhong
authors.forename: C
authors.initials: C
authors.lastname: Cheers
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D017635:Clonal Anergy / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009162:Mycobacterium avium / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014376:Tuberculosis / Q000276:immunology* / Q000401:mortality* / Q000473:pathology / Q000503:physiopathology
chemical_list: D007371:Interferon-gamma