Tuberculous pleurisy drives marked effector responses of gamma delta, CD4(+), and CD8(+) T cell subpopulations in humans

摘要

Although tuberculous pleurisy (TP) presumably involves a hypersensitivity reaction, there is limited evidence indicating overreactive effector responses of gamma delta T cells and ab T cells and their interrelation with Foxp3(+) T-regs in pleural and other compartments. We found that TP induced reciprocal representations of Foxp3(+) T-regs and Mtb phosphoantigen-specific V gamma 2V delta 2 T cells in different anatomic compartments. Patients with TP exhibited appreciable numbers of "proliferating" Ki-67(+) V gamma 2V delta 2 T cells in the airway where Foxp3(+) T-regs were not dominant, whereas striking increases in Foxp3(+) T-regs in the blood and pleural compartments coincided with low frequencies of V gamma 2V delta 2 T cells. Interestingly, anti-tuberculosis chemotherapy control of Mtb infection in patients with TP reversed reciprocal representations of Foxp3(+) T-regs and proliferating V gamma 2V delta 2 T cells. Surprisingly, despite high-level Foxp3(+) T-regs, TP appeared to drive overreactive responses of IFN-gamma-producing V gamma 2V delta 2, CD4(+) CD25(+), andCD8(+) CD25(+) T effector subpopulations, whereas IL-22-producing V gamma 2V delta 2 T cells increased subtly. Th1 effector responses were sustained despite remarkable declines in Foxp3(+) T-regs at 1 mo after the treatment. Overreactive T effector responses of Mtbreactive gamma delta T cells, ab CD25(+) CD4(+), and CD25(+) CD8(+) T cell subpopulations appear to be immune features for TP. Increased Foxp3(+) T-regs might be responsive to overreactive TP but unable to influence T effector responses despite having an inverse relation with proliferating V gamma 2V delta 2 T cells.

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