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Identification of a human Th1-like IFNγ-secreting Treg subtype deriving from effector T cells.
- Source :
-
Journal of autoimmunity [J Autoimmun] 2012 Dec; Vol. 39 (4), pp. 377-87. Date of Electronic Publication: 2012 Jul 22. - Publication Year :
- 2012
-
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.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Antigens, CD genetics
Antigens, CD immunology
Biomarkers metabolism
Cell Communication genetics
Cell Communication immunology
Cell Proliferation
Cells, Cultured
Chronic Disease
Forkhead Transcription Factors genetics
Forkhead Transcription Factors immunology
Gene Expression Regulation immunology
Humans
Immunologic Memory
Interferon-gamma genetics
Lymphocyte Activation
Signal Transduction
T-Lymphocytes, Helper-Inducer metabolism
T-Lymphocytes, Regulatory classification
T-Lymphocytes, Regulatory metabolism
Tonsillitis genetics
Tonsillitis pathology
Cell Differentiation immunology
Immunity, Cellular
Interferon-gamma immunology
T-Lymphocytes, Helper-Inducer immunology
T-Lymphocytes, Regulatory immunology
Tonsillitis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9157
- Volume :
- 39
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of autoimmunity
- Publication Type :
- Academic Journal
- Accession number :
- 22824211
- Full Text :
- https://doi.org/10.1016/j.jaut.2012.06.004