International Immunology Advance Access originally published online on March 15, 2006
International Immunology 2006 18(4):555-563; doi:10.1093/intimm/dxh396
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Differential expression of CD126 and CD130 mediates different STAT-3 phosphorylation in CD4+CD25– and CD25high regulatory T cells
1 Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, Michaelisstrasse 5, D-24105 Kiel, Germany
2 Institute of Biochemistry, Christian-Albrechts-University, Kiel, Germany
Correspondence to: D. Kabelitz; E-mail: kabelitz{at}immunologie.uni-kiel.de
IL-6 is a pleiotropic cytokine involved in T-lymphocyte biology. Following IL-6 binding, the soluble IL-6R (CD126)–IL-6 complex can directly activate cells that express the signal-transducing gp130 (CD130) molecule, which mediates two distinct signals, mitogenesis by mitogen-activated protein kinase (MAPK) activation and anti-apoptosis by signal transducer and activator of transcription 3 (STAT-3) activation. This ‘trans-signaling’, also mediated by the soluble CD126/IL-6 fusion protein hyper-IL-6 (H-IL-6), contributes to the perpetuation of autoimmune diseases such as Morbus Crohn or rheumatoid arthritis. On the other hand, the homeostasis of cellular immune reactions and its failure leading to autoimmune diseases are critically controlled by regulatory T cells (Tregs). Here, we investigated the differential expression of CD126 and CD130 on subsets of human leukocytes in blood, tonsil and spleen. Among CD4+ T cells, differential expression of CD126 and CD130 was observed on the basis of CD25 expression. CD4+CD25– T cells were strongly CD126+ and CD130+, whereas CD25high Tregs expressed CD126 but little CD130. Both CD126 and CD130 were down-modulated on CD4+CD25– T cells following ligand binding, whereas only marginal modulation was observed on Tregs. Interestingly, we observed a correlation between CD126 and CD130 expression with STAT-3 phosphorylation in CD4+CD25– T cells compared with Tregs after stimulation with IL-6 or H-IL-6, whereas the MAPK extracellular signal-regulated kinase 1/2 were not activated by CD130 dimerization. The differential expression of CD126 and CD130 and subsequent STAT-3 phosphorylation might be relevant for the recently described role of IL-6 in the control of Treg activity.
Keywords: human, signal transduction, T lymphocytes, tolerance/suppression/anergy
* These authors contributed equally to this work.
Transmitting editor: A. Radbruch
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