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Mycobacterium tuberculosis-specific CD8 super(+) T cells are functionally and phenotypically different between latent infection and active disease

Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8 super(+) T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb-specific CD8 super(+) T cells in 326 subjects with latent Mtb infection (L...

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Published in:European journal of immunology 2013-06, Vol.43 (6), p.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
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Language:English
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Summary:Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8 super(+) T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb-specific CD8 super(+) T cells in 326 subjects with latent Mtb infection (LTBI) or active TB disease (TB). Mtb-specific CD8 super(+) T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. Mtb-specific CD8 super(+) T cells in LTBI subjects were mostly T sub(EMRA) cells (CD45RA super(+)CCR7 super(-)), coexpressing 2B4 and CD160, and in TB patients were mostly T sub(EM) cells (CD45RA super(-)CCR7 super(- )), expressing 2B4 but lacking PD-1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, Mtb-specific CD8 super(+) T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro-expanded Mtb-specific CD8 super(+) T cells expressed perforin and granulysin. Finally, Mtb-specific CD8 super(+) T-cell responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. Mtb-specific CD8 super(+) 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 super(+) T-cell responses. These results provide new insights in the interaction between Mtb and the host immune response.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201243262