Mycobacterium tuberculosis‐specific CD8+ 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+ 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.