Submitted June 12, 2008
Accepted September 13, 2008
Phosphoantigen-activated V
2V
2 T cells antagonize IL-2-induced CD4+CD25+Foxp3+ T regulatory cells
Guangming Gong, Lingyun Shao, Yunqi Wang, Crystal Y Chen, Dan Huang, Shuyu Yao, Ximei Zhan, Helene Sicard, Richard Wang, and Zheng W Chen*
Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois at Chicago, Chicago, IL, United States
Department of Parasitology, Zongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
Innate Pharma, Marseille, France
* Corresponding author; email: zchen{at}uic.edu.
While Foxp3+ T regulatory cells (Treg) are well documented for their ability to suppress various immune cells, T cell subsets capable of counteracting Treg have not been demonstrated. Here, we assessed phosphoantigen-activated V
2V
2 T cells for the ability to interplay with Treg 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 V2V2 T cells. Surprisingly, activation of V2V2 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 V2V2 T cells by phosphoantigen+IL-2 down-regulated IL-2-induced expansion of CD4+CD25+Foxp3+ T cells. Interestingly, anti-IFN- neutralizing antibody, not anti-TGF-
or anti-IL-4, reduced the ability of activated V2V2 T-cells to down-regulate Treg, suggesting that autocrine IFN- and its network contributed to V2V2 T cells' antagonizing effects. Furthermore, activation of V2V2 T cells by Picostim+IL-2 treatment appeared to reverse Treg-driven suppression of immune responses of phosphoantigen-specific IFN+ or perforin+ V2V2 T cells and PPD-specific IFN+ 
T cells. Thus, phosphoantigen-activation of V2V2 T cells antagonizes IL-2-induced expansion of Treg and subsequent suppression of Ag-specific antimicrobial T cell responses in mycobacterial infection.
