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

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.

• Authors: Chan-Yu Lin, Ann Kift-Morgan, Bernhard Moser, Nicholas Topley, Matthias Eberl
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 28 Issue 7 Pg. 1743-50 (Jul 2013) ISSN: 1460-2385 [Electronic] England
• PMID: 23355626 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-hydroxy-3-methylbut-2-enyl pyrophosphate
• Cytokines
• Diphosphates
• Inflammation Mediators
• Receptors, Antigen, T-Cell, gamma-delta
• Transforming Growth Factor beta

Topics

• Blotting, Western
• Cells, Cultured
• Cytokines (metabolism)
• Diphosphates (pharmacology)
• Enzyme-Linked Immunosorbent Assay
• Epithelium (drug effects, immunology, metabolism)
• Humans
• Inflammation Mediators (metabolism)
• Lymphocyte Activation
• Omentum (drug effects, immunology, metabolism)
• Peritoneal Dialysis
• Receptors, Antigen, T-Cell, gamma-delta (immunology, metabolism)
• T-Lymphocyte Subsets (cytology, drug effects, immunology)
• Transforming Growth Factor beta (metabolism)