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Suppression of pro-inflammatory T-cell responses by human mesothelial cells

Lin, Chan-Yu, Kift-Morgan, Ann Patricia, Moser, Bernhard, Topley, Nicholas and Eberl, Matthias 2013. Suppression of pro-inflammatory T-cell responses by human mesothelial cells. Nephrology Dialysis Transplantation 28 (7) , pp. 1743-1750. 10.1093/ndt/gfs612

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Abstract

BACKGROUND: Human γδ T cells reactive to the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) contribute to acute inflammatory responses. We have previously shown that peritoneal dialysis (PD)-associated infections with HMB-PP producing bacteria are characterized by locally elevated γδ T-cell frequencies and poorer clinical outcome compared with HMB-PP negative infections, implying that γδ T cells may be of diagnostic, prognostic and therapeutic value in acute disease. The regulation by local tissue cells of these potentially detrimental γδ T-cell responses remains to be investigated. METHODS: Freshly isolated γδ or αβ T cells were cultured with primary mesothelial cells derived from omental tissue, or with mesothelial cell-conditioned medium. Stimulation of cytokine production and proliferation by peripheral T cells in response to HMB-PP or CD3/CD28 beads was assessed by flow cytometry. RESULTS: Resting mesothelial cells were potent suppressors of pro-inflammatory γδ T cells as well as CD4+ and CD8+ αβ T cells. The suppression of γδ T-cell responses was mediated through soluble factors released by primary mesothelial cells and could be counteracted by SB-431542, a selective inhibitor of TGF-β and activin signalling. Recombinant TGF-β1 but not activin-A mimicked the mesothelial cell-mediated suppression of γδ T-cell responses to HMB-PP. CONCLUSIONS: The present findings indicate an important regulatory function of mesothelial cells in the peritoneal cavity by dampening pro-inflammatory T-cell responses, which may help preserve the tissue integrity of the peritoneal membrane in the steady state and possibly during the resolution of acute inflammation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QH Natural history > QH426 Genetics
Q Science > QR Microbiology > QR180 Immunology
Uncontrolled Keywords: Blotting, Western; Cells, Cultured; Cytokines; Diphosphates; Enzyme-Linked Immunosorbent Assay; Epithelium; Humans; Inflammation Mediators; Lymphocyte Activation; Omentum; Peritoneal Dialysis; Receptors, Antigen, T-Cell, gamma-delta; T-Lymphocyte Subsets; Transforming Growth Factor beta
Publisher: Oxford University Press
ISSN: 0931-0509
Date of Acceptance: 17 December 2012
Last Modified: 22 Dec 2017 20:22
URI: http://orca.cf.ac.uk/id/eprint/74164

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