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

Chan Yu Lin, Ann Kift-Morgan, Bernhard Moser, Nicholas Topley, Matthias Eberl*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

5 Scopus citations

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.

Original languageEnglish
Pages (from-to)1743-1750
Number of pages8
JournalNephrology Dialysis Transplantation
Volume28
Issue number7
DOIs
StatePublished - 07 2013
Externally publishedYes

Keywords

  • Inflammation
  • Mesothelial cells
  • Peritoneal dialysis
  • TGF-β
  • γδ T lymphocytes

Fingerprint

Dive into the research topics of 'Suppression of pro-inflammatory T-cell responses by human mesothelial cells'. Together they form a unique fingerprint.

Cite this