Mycobacterium tuberculosis‐specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease

• Published in: European journal of immunology Vol. 43; no. 6; pp. 1568 - 1577
• Main Authors: Rozot, Virginie, Vigano, Selena, Mazza‐Stalder, Jesica, Idrizi, Elita, Day, Cheryl L., Perreau, Matthieu, Lazor‐Blanchet, Catherine, Petruccioli, Elisa, Hanekom, Willem, Goletti, Delia, Bart, Pierre‐Alexandre, Nicod, Laurent, Pantaleo, Giuseppe, Harari, Alexandre
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.06.2013
• Subjects: Active TB disease; Acute Disease; Antigens, CD - metabolism; CD8-Positive T-Lymphocytes - immunology; Cell Proliferation; Cells, Cultured; Cytokines - metabolism; Cytotoxicity; Functional profile; GPI-Linked Proteins - metabolism; Humans; Immunology; Immunophenotyping; Latent Mtb infection; Latent Tuberculosis - immunology; Lymphocytes; Mtb‐specific CD8+ T cells; Mycobacterium tuberculosis - immunology; Programmed Cell Death 1 Receptor - metabolism; Receptors, Immunologic - metabolism; Signaling Lymphocytic Activation Molecule Family; T cell receptors; T-Lymphocyte Subsets - immunology; Tuberculosis; Tuberculosis, Pulmonary - immunology
• ISSN: 0014-2980; 1521-4141; 1521-4141
• DOI: 10.1002/eji.201243262

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 TEMRA 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.