Phosphoantigen-activated V gamma 2V delta 2 T cells antagonize IL-2-induced CD4+CD25+Foxp3+ T regulatory cells in mycobacterial infection.

Abstract

Although Foxp3(+) T regulatory cells (Tregs) are well documented for their ability to suppress various immune cells, T-cell subsets capable of counteracting Tregs have not been demonstrated. Here, we assessed phosphoantigen-activated Vgamma2Vdelta2 T cells for the ability to interplay with Tregs in the context of mycobacterial infection. A short-term IL-2 treatment regimen induced marked expansion of CD4(+)CD25(+)Foxp3(+) T cells and subsequent suppression of mycobacterium-driven increases in numbers of Vgamma2Vdelta2 T cells. Surprisingly, activation of Vgamma2Vdelta2 T cells by adding phosphoantigen Picostim to the IL-2 treatment regimen down-regulated IL-2-induced expansion of CD4(+)CD25(+)Foxp3(+) T cells. Consistently, in vitro activation of Vgamma2Vdelta2 T cells by phosphoantigen plus IL-2 down-regulated IL-2-induced expansion of CD4(+)CD25(+)Foxp3(+) T cells. Interestingly, anti-IFN-gamma-neutralizing antibody, not anti-TGF-beta or anti-IL-4, reduced the ability of activated Vgamma2Vdelta2 T cells to down-regulate Tregs, suggesting that autocrine IFN-gamma and its network contributed to Vgamma2Vdelta2 T cells' antagonizing effects. Furthermore, activation of Vgamma2Vdelta2 T cells by Picostim plus IL-2 treatment appeared to reverse Treg-driven suppression of immune responses of phosphoantigen-specific IFNgamma(+) or perforin(+) Vgamma2Vdelta2 T cells and PPD-specific IFNgamma(+)alphabeta T cells. Thus, phos-phoantigen activation of Vgamma2Vdelta2 T cells antagonizes IL-2-induced expansion of Tregs and subsequent suppression of Ag-specific antimicrobial T-cell responses in mycobacterial infection.

DOI: 10.1182/blood-2008-06-162792

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@article{Gong2009PhosphoantigenactivatedVG, title={Phosphoantigen-activated V gamma 2V delta 2 T cells antagonize IL-2-induced CD4+CD25+Foxp3+ T regulatory cells in mycobacterial infection.}, author={Guangming Gong and Lingyun Shao and Yunqi Wang and Crystal Chen and Dan Huang and Shuyu Yao and Ximei Zhan and H{\'e}l{\`e}ne Sicard and Richard C. Wang and Zheng Chen}, journal={Blood}, year={2009}, volume={113 4}, pages={837-45} }