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

2013; Wiley; Volume: 43; Issue: 6 Linguagem: Inglês

10.1002/eji.201243262

1521-4141

Virginie Rozot, Selena Viganó, Jesica Mazza‐Stalder, Elita Idrizi, Cheryl L. Day, Matthieu Perreau, Catherine Lazor‐Blanchet, Elisa Petruccioli, Willem A. Hanekom, Delia Goletti, Pierre‐Alexandre Bart, Laurent Nicod, Giuseppe Pantaleo, Alexandre Harari,

Immune Cell Function and Interaction

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.