Although tuberculous pleurisy (TP) presumably involves a hypersensitivity reaction, there is limited evidence indicating overreactive effector responses of γδ T cells and αβ T cells and their interrelation with Foxp3+ Tregs in pleural and other compartments. We found that TP induced reciprocal representations of Foxp3+ Tregs and Mtb phosphoantigen-specific Vγ2Vδ2 T cells in different anatomic compartments. Patients with TP exhibited appreciable numbers of "proliferating" Ki-67+ Vγ2Vδ2 T cells in the airway where Foxp3+ Tregs were not dominant, whereas striking increases in Foxp3+ Tregs in the blood and pleural compartments coincided with low frequencies o... More
Although tuberculous pleurisy (TP) presumably involves a hypersensitivity reaction, there is limited evidence indicating overreactive effector responses of γδ T cells and αβ T cells and their interrelation with Foxp3+ Tregs in pleural and other compartments. We found that TP induced reciprocal representations of Foxp3+ Tregs and Mtb phosphoantigen-specific Vγ2Vδ2 T cells in different anatomic compartments. Patients with TP exhibited appreciable numbers of "proliferating" Ki-67+ Vγ2Vδ2 T cells in the airway where Foxp3+ Tregs were not dominant, whereas striking increases in Foxp3+ Tregs in the blood and pleural compartments coincided with low frequencies of Vγ2Vδ2 T cells. Interestingly, anti-tuberculosis chemotherapy control of Mtb infection in patients with TP reversed reciprocal representations of Foxp3+ Tregs and proliferating Vγ2Vδ2 T cells. Surprisingly, despite high-level Foxp3+ Tregs, TP appeared to drive overreactive responses of IFN-γ-producing Vγ2Vδ2, CD4+CD25+, and CD8+CD25+ T effector subpopulations, whereas IL-22-producing Vγ2Vδ2 T cells increased subtly. Th1 effector responses were sustained despite remarkable declines in Foxp3+ Tregs at 1 mo after the treatment. Overreactive T effector responses of Mtb-reactive γδ T cells, αβ CD25+CD4+, and CD25+CD8+ T cell subpopulations appear to be immune features for TP. Increased Foxp3+ Tregs might be responsive to overreactive TP but unable to influence T effector responses despite having an inverse relation with proliferating Vγ2Vδ2 T cells.
