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Blood, 22 January 2009, Vol. 113, No. 4, pp. 837-845.
Prepublished online as a Blood First Edition Paper on November 3, 2008; DOI 10.1182/blood-2008-06-162792.
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IMMUNOBIOLOGY
Phosphoantigen-activated V 2V 2 T cells antagonize IL-2–induced CD4+CD25+Foxp3+ T regulatory cells in mycobacterial infection
Guangming Gong1,2,*,
Lingyun Shao1,*,
Yunqi Wang1,*,
Crystal Y. Chen1,
Dan Huang1,
Shuyu Yao1,
Ximei Zhan2,
Helene Sicard3,
Richard Wang1, and
Zheng W. Chen1
1 Department of Microbiology and Immunology, Center for Primate Biomedical Research, College of Medicine, University of Illinois at Chicago;
2 Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China; and
3 Innate Pharma, Marseille, France
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 V 2V 2 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 V 2V 2 T cells. Surprisingly, activation of V 2V 2 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 V 2V 2 T cells by phosphoantigen plus IL-2 down-regulated IL-2–induced expansion of CD4+CD25+Foxp3+ T cells. Interestingly, anti–IFN- –neutralizing antibody, not anti–TGF-β or anti–IL-4, reduced the ability of activated V 2V 2 T cells to down-regulate Tregs, suggesting that autocrine IFN- and its network contributed to V 2V 2 T cells' antagonizing effects. Furthermore, activation of V 2V 2 T cells by Picostim plus IL-2 treatment appeared to reverse Treg-driven suppression of immune responses of phosphoantigen-specific IFN + or perforin+ V 2V 2 T cells and PPD-specific IFN + β T cells. Thus, phos-phoantigen activation of V 2V 2 T cells antagonizes IL-2–induced expansion of Tregs and subsequent suppression of Ag-specific antimicrobial T-cell responses in mycobacterial infection.

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