title: Dissemination of mycobacteria to the thymus renders newly generated T cells tolerant to the invading pathogen.
abstract: The ability of the thymus to generate a population of T cells that is, for the most part, self-restricted and self-tolerant depends to a great extent on the Ags encountered during differentiation. We recently showed that mycobacteria disseminate to the thymus, which raised the questions of how mycobacteria within the thymus influence T cell differentiation and whether such an effect impacts host-pathogen interactions. Athymic nude mice were reconstituted with thymic grafts from Mycobacterium avium-infected or control noninfected donors. T cells generated from thymi of infected donors seemed generally normal, because they retained the ability to reconstitute the periphery and to respond to unspecific stimuli in vitro as well as to antigenic stimulation with third-party Ags, such as OVA, upon in vivo immunization. However, these cells were unable to mount a protective immune response against a challenge with M. avium. The observation that thymic infection interferes with T cell differentiation, generating T cells that are tolerant to pathogen-specific Ags, is of relevance to understand the immune response during chronic persistent infections. In addition, it has potential implications for the repertoire of T cells generated in patients with a mycobacterial infection recovering from severe lymphopenia, such as patients coinfected with HIV and receiving antiretroviral therapy.
authors: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.
authors: Claudia
authors: C
authors: Nobrega
authors: Susana
authors: S
authors: Roque
authors: Cláudio
authors: C
authors: Nunes-Alves
authors: Angela
authors: A
authors: Coelho
authors: Irene
authors: I
authors: Medeiros
authors: António Gil
authors: AG
authors: Castro
authors: Rui
authors: R
authors: Appelberg
authors: Margarida
authors: M
authors: Correia-Neves
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007091:Image Processing, Computer-Assisted; D007108:Immune Tolerance / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D009162:Mycobacterium avium / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology / Q000382:microbiology*; D014376:Tuberculosis / Q000276:immunology* / Q000662:veterinary