Mycobacterium tuberculosis‐specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease. Issue 6 (21st June 2013)

• Record Type: Journal Article
• 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
• Is Part Of: European journal of immunology. Volume 43:Issue 6(2013:Jun.)
• Page Start: 1568
• Page End: 1577
• Publication Date: 2013-06-21
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201243262
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Protective immunity to <italic>Mycobacterium tuberculosis</italic> (<italic>Mtb</italic>) remains poorly understood and the role of <italic>Mtb</italic>‐specific CD8<sup>+</sup> T cells is controversial. Here we performed a broad phenotypic and functional characterization of <italic>Mtb</italic>‐specific CD8<sup>+</sup> T cells in 326 subjects with latent <italic>Mtb</italic> infection (LTBI) or active TB disease (TB). <italic>Mtb</italic>‐specific CD8<sup>+</sup> T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. <italic>Mtb</italic>‐specific CD8<sup>+</sup> T cells in LTBI subjects were mostly T<sub>EMRA</sub> cells (CD45RA<sup>+</sup>CCR7<sup>−</sup>), coexpressing 2B4 and CD160, and in TB patients were mostly T<sub>EM</sub> cells (CD45RA<sup>−</sup>CCR7<sup>−</sup>), expressing 2B4 but lacking PD‐1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, <italic>Mtb</italic>‐specific CD8<sup>+</sup> T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro‐expanded <italic>Mtb</italic>‐specific CD8<sup>+</sup> T cells expressed perforin and granulysin. Finally, <italic>Mtb</italic>‐specific CD8<sup>+</sup> T‐cell responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. <italic>Mtb</italic>‐specific CD8<sup>+</sup> T‐cell proliferation was also greater in patients with extrapulmonary compared with pulmonary TB. Thus, the activity of <italic>Mtb</italic> infection and clinical presentation are associated with distinct profiles of <italic>Mtb</italic>‐specific CD8<sup>+</sup> T‐cell responses. These results provide new insights in the interaction between <italic>Mtb</italic> and the host immune response.</p> </abstract>