title: Mycobacterium tuberculosis-specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease.
abstract: Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8(+) T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb-specific CD8(+) T cells in 326 subjects with latent Mtb infection (LTBI) or active TB disease (TB). Mtb-specific CD8(+) T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. Mtb-specific CD8(+) T cells in LTBI subjects were mostly T EMRA cells (CD45RA(+) CCR7(-)), coexpressing 2B4 and CD160, and in TB patients were mostly TEM cells (CD45RA(-) CCR7(-)), expressing 2B4 but lacking PD-1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, Mtb-specific CD8(+) T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro-expanded Mtb-specific CD8(+) T cells expressed perforin and granulysin. Finally, Mtb-specific CD8(+) T-cell responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. Mtb-specific CD8(+) T-cell proliferation was also greater in patients with extrapulmonary compared with pulmonary TB. Thus, the activity of Mtb infection and clinical presentation are associated with distinct profiles of Mtb-specific CD8(+) T-cell responses. These results provide new insights in the interaction between Mtb and the host immune response.
authors: Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
authors: Virginie
authors: V
authors: Rozot
authors: Selena
authors: S
authors: Vigano
authors: Jesica
authors: J
authors: Mazza-Stalder
authors: Elita
authors: E
authors: Idrizi
authors: Cheryl L
authors: CL
authors: Day
authors: Matthieu
authors: M
authors: Perreau
authors: Catherine
authors: C
authors: Lazor-Blanchet
authors: Elisa
authors: E
authors: Petruccioli
authors: Willem
authors: W
authors: Hanekom
authors: Delia
authors: D
authors: Goletti
authors: Pierre-Alexandre
authors: PA
authors: Bart
authors: Laurent
authors: L
authors: Nicod
authors: Giuseppe
authors: G
authors: Pantaleo
authors: Alexandre
authors: A
authors: Harari
mesh_terms: D000208:Acute Disease; D015703:Antigens, CD / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D055985:Latent Tuberculosis / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D000071176:Signaling Lymphocytic Activation Molecule Family; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C114505:CD160 protein, human; C084093:CD244 protein, human; D016207:Cytokines; D058851:GPI-Linked Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family