Identification of a human Th1-like IFNγ-secreting Treg subtype deriving from effector T cells

• Verfasst von: Venigalla, Ram Kumar Chowdary [VerfasserIn]
• Verfasst von: Guttikonda, Padmaja Jayathi [VerfasserIn]
• Verfasst von: Eckstein, Volker [VerfasserIn]
• Verfasst von: Ho, Anthony Dick [VerfasserIn]
• Verfasst von: Sertel, Serkan [VerfasserIn]
• Verfasst von: Lorenz, Hanns-Martin [VerfasserIn]
• Verfasst von: Tretter, Theresa [VerfasserIn]
• Titel: Identification of a human Th1-like IFNγ-secreting Treg subtype deriving from effector T cells
• Verf.angabe: Ram Kumar Chowdary Venigalla, Padmaja Jayathi Guttikonda, Volker Eckstein, Anthony D. Ho, Serkan Sertel, Hanns-Martin Lorenz, Theresa Tretter
• E-Jahr: 2012
• Jahr: 21 July 2012
• Umfang: 11 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 15.10.2018
• Titel Quelle: Enthalten in: Journal of autoimmunity
• Ort Quelle: London : Academic Press, 1988
• Jahr Quelle: 2012
• Band/Heft Quelle: 39(2012), 4, Seite 377-387
• ISSN Quelle: 1095-9157
• DOI: doi:10.1016/j.jaut.2012.06.004
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adaptive Treg
• Sach-SW: IFN-gamma
• Sach-SW: Immune regulation
• Sach-SW: T helper cells
• Sach-SW: Th1
• K10plus-PPN: 1581878982

Abstract

Characteristics and function of effector T-cells with regulatory properties (induced Treg, “iTreg”) in humans are ill defined. Here we report that a proportion of activated, initially CD4(+)CD25(−)CD127(+) effector T-cells from human peripheral blood can convert into T-cells with regulatory activity while concomitantly secreting IFNγ. Upon short-term culture in vitro these cells expressed a panel of common Treg markers, including FOXP3, CD25, GITR, HLA-DR and CTLA-4 in parallel with the Th1-specific transcription factor T-bet. Despite their own IFNγ secretion they effectively suppressed IFNγ secretion in effector T cells in parallel with inhibition of their proliferation. Highly purified IFNγ(+)iTreg shared many functional properties with nTreg: Their suppressive activity was antigen-independent, contact-mediated and cytokine-independent. Of note, in contrast to nTreg an inhibitor of TGF-β1 signalling promoted the proliferation of IFNγ(+)iTreg, without abrogating their suppressive function. In addition in vivo in tonsils of patients with chronic tonsillitis an IFNγ-secreting subpopulation of the CD4(+)CD25(−)CD127(+)CD45RA(−) memory T helper cell population was detected, which exhibited regulatory properties as well. Our results support the existence of Th1-like adaptive Tregs in humans that express a robust regulatory phenotype, comparable to nTreg and at the same time share characteristics of Th1 cells. According to our in vitro data IFNγ(+)iTreg can emerge from activated effector T cells and downregulate Th1-mediated immune responses, supporting the hypothesis of effector T cell plasticity as a means for proper initiation and self regulation of inflammatory processes. This report characterizes a new subpopulation of human adaptive regulatory T-cells that derive from effector Th-cells and concomitantly express Th1-specific T-bet and IFNγ with Foxp3.