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Clonal Expansions of CD8+ T Cells with IL-10 Secreting Capacity Occur during Chronic Mycobacterium tuberculosis Infection. e58612
The exact role of CD8+ T cells during Mycobacterium tuberculosis (Mtb) infection has been heavily debated, yet it is generally accepted that CD8+ T cells contribute to protection against Mtb. In this study, however, we show that the Mtb-susceptible CBA/J mouse strain accumulates large numbers of CD8...
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Published in: | PloS one 2013-03, Vol.8 (3) |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | The exact role of CD8+ T cells during Mycobacterium tuberculosis (Mtb) infection has been heavily debated, yet it is generally accepted that CD8+ T cells contribute to protection against Mtb. In this study, however, we show that the Mtb-susceptible CBA/J mouse strain accumulates large numbers of CD8+ T cells in the lung as infection progresses, and that these cells display a dysfunctional and immunosuppressive phenotype (PD-1+, Tim-3+, CD122+). CD8+ T cell expansions from the lungs of Mtb-infected CBA/J mice were also capable of secreting the immunosuppressive cytokine interleukin-10 (IL-10), although in vivo CD8+ T cell depletion did not significantly alter Mtb burden. Further analysis revealed that pulmonary CD8+ T cells from Mtb-infected CBA/J mice were clonally expanded, preferentially expressing T cell receptor (TcR) V beta chain 8 (8.2, 8.3) or V beta 14. Although V beta 8+ CD8+ T cells were responsible for the majority of IL-10 production, in vivo depletion of V beta 8+ did not significantly change the outcome of Mtb infection, which we hypothesize was a consequence of their dual IL-10/IFN- gamma secreting profiles. Our data demonstrate that IL-10-secreting CD8+ T cells can arise during chronic Mtb infection, although the significance of this T cell population in tuberculosis pathogenesis remains unclear. |
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ISSN: | 1932-6203 |
DOI: | 10.1371/journal.pone.0058612 |