Identification of a human Th1-like IFNγ-secreting Treg subtype deriving from effector T cells
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...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
21 July 2012
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| In: |
Journal of autoimmunity
Year: 2012, Volume: 39, Issue: 4, Pages: 377-387 |
| ISSN: | 1095-9157 |
| DOI: | 10.1016/j.jaut.2012.06.004 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.jaut.2012.06.004 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0896841112000959 
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| Author Notes: | Ram Kumar Chowdary Venigalla, Padmaja Jayathi Guttikonda, Volker Eckstein, Anthony D. Ho, Serkan Sertel, Hanns-Martin Lorenz, Theresa Tretter |
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| 245 | 1 | 0 | |a Identification of a human Th1-like IFNγ-secreting Treg subtype deriving from effector T cells |c Ram Kumar Chowdary Venigalla, Padmaja Jayathi Guttikonda, Volker Eckstein, Anthony D. Ho, Serkan Sertel, Hanns-Martin Lorenz, Theresa Tretter |
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| 520 | |a 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. | ||
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