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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 |
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Main Authors: | , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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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. |
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ISSN: | 0014-2980 1521-4141 |
DOI: | 10.1002/eji.201243262 |