Phosphoantigen-activated Vγ2Vδ2 T cells antagonize IL-2–induced CD4+CD25+Foxp3+ T regulatory cells in mycobacterial infection

Content Provider	Scilit
Author	Gong, Guangming Shao, Lingyun Wang, Yunqi Chen, Crystal Y. Huang, Dan Yao, Shuyu Zhan, Ximei Sicard, Helene Wang, Richard Chen, Zheng W.
Copyright Year	2009
Description	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 Vγ2Vδ2 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 Vγ2Vδ2 T cells. Surprisingly, activation of Vγ2Vδ2 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 Vγ2Vδ2 T cells by phosphoantigen plus IL-2 down-regulated IL-2–induced expansion of CD4+CD25+Foxp3+ T cells. Interestingly, anti–IFN-γ–neutralizing antibody, not anti–TGF-β or anti–IL-4, reduced the ability of activated Vγ2Vδ2 T cells to down-regulate Tregs, suggesting that autocrine IFN-γ and its network contributed to Vγ2Vδ2 T cells' antagonizing effects. Furthermore, activation of Vγ2Vδ2 T cells by Picostim plus IL-2 treatment appeared to reverse Treg-driven suppression of immune responses of phosphoantigen-specific IFNγ+ or perforin+ Vγ2Vδ2 T cells and PPD-specific IFNγ+αβ T cells. Thus, phos-phoantigen activation of Vγ2Vδ2 T cells antagonizes IL-2–induced expansion of Tregs and subsequent suppression of Ag-specific antimicrobial T-cell responses in mycobacterial infection.
Related Links	https://ashpublications.org/blood/article-pdf/113/4/837/1312074/zh800409000837.pdf
Ending Page	845
Page Count	9
Starting Page	837
DOI	10.1182/blood-2008-06-162792
Journal	Blood
Issue Number	4
Volume Number	113
Language	English
Publisher	American Society of Hematology
Publisher Date	2009-01-22
Access Restriction	Open
Subject Keyword	Immunology Treatment Foxp3 Tregs Vγ2vδ2 T Cells Phosphoantigen Antagonizing Antibody Cd25 Cd4 Journal: Blood (Vol- 79, Issue- 4)
Content Type	Text
Resource Type	Article