title: 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.
authors.affiliation: Department of Microbiology and Immunology, Center for Primate Biomedical Research, College of Medicine, University of Illinois at Chicago, IL, USA.
authors.forename: Guangming
authors.initials: G
authors.lastname: Gong
authors.forename: Lingyun
authors.initials: L
authors.lastname: Shao
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Wang
authors.forename: Crystal Y
authors.initials: CY
authors.lastname: Chen
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: Shuyu
authors.initials: S
authors.lastname: Yao
authors.forename: Ximei
authors.initials: X
authors.lastname: Zhan
authors.forename: Helene
authors.initials: H
authors.lastname: Sicard
authors.forename: Richard
authors.initials: R
authors.lastname: Wang
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001426:Bacterial Proteins / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D051858:Forkhead Transcription Factors / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D008252:Macaca fascicularis; D009164:Mycobacterium Infections / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D000906:Antibodies; D001426:Bacterial Proteins; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D010446:Peptide Fragments; D010750:Phosphoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016212:Transforming Growth Factor beta; C069261:interferon gamma (1-39); D015847:Interleukin-4; D007371:Interferon-gamma