title: Mycobacterium tuberculosis-specific CD8+ T cells preferentially recognize heavily infected cells.
abstract: Both CD4+ and CD8+ T cells are important for successful immunity to tuberculosis and have redundant effector functions, such as cytolysis and release of potent antimycobacterial cytokines such as interferon-gamma and tumor necrosis factor-alpha. We hypothesized that CD8+ T cells play a unique role in host defense to Mycobacterium tuberculosis infection as well. Possibilities include preferential and/or enhanced release of granular constituents and/or preferential recognition of heavily infected cells. Utilizing human, Mycobacterium tuberculosis-specific, CD4+ and CD8+ T cell clones, we demonstrate that, after recognition of antigen-presenting cells displaying peptide antigen, CD4+ T cells preferentially release interferon-gamma, whereas CD8+ T cells preferentially lyse antigen-presenting cells. Furthermore, utilizing dendritic cells infected with Mycobacterium tuberculosis expressing green fluorescent protein, we show that CD8+ T cells preferentially recognize heavily infected cells that constitute the minority of infected cells. These data support the hypothesis that the central role of CD8+ T cells in the control of infection with Mycobacterium tuberculosis may be that of surveillance; in essence, recognition of cells in which the containment of Mycobacterium tuberculosis is no longer effective.
authors.affiliation: Department of Pediatrics, Oregon Health and Science University, Portland, Oregon 97239, USA. lewinsde@OHSU.edu
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Lewinsohn
authors.forename: Amy S
authors.initials: AS
authors.lastname: Heinzel
authors.forename: James M
authors.initials: JM
authors.lastname: Gardner
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhu
authors.forename: Mark R
authors.initials: MR
authors.lastname: Alderson
authors.forename: David M
authors.initials: DM
authors.lastname: Lewinsohn
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005089:Exocytosis / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D059909:HLA-B14 Antigen; D059948:HLA-B44 Antigen; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D000097625:HLA-E Antigens
chemical_list: D000942:Antigens, Bacterial; D006680:HLA Antigens; D015235:HLA-B Antigens; D059909:HLA-B14 Antigen; D059948:HLA-B44 Antigen; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma; D000097625:HLA-E Antigens; C072681:Mycobacterium tuberculosis antigens