A subset of IL-10-producing gammadelta T cells protect the liver from Listeria-elicited, CD8(+) T cell-mediated injury

Katherine A Rhodes, Elizabeth M Andrew, Darren J Newton, Daniela Tramonti, Simon R Carding

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

Abstract

Although gammadelta T cells play a role in protecting tissues from pathogen-elicited damage to bacterial, viral and parasitic pathogens, the mechanisms involved in the damage and in the protection have not been clearly elucidated. This has been addressed using a murine model of listeriosis, which in mice lacking gammadelta T cells (TCRdelta(-/-)) is characterised by severe and extensive immune-mediated hepatic necrosis. We show that these hepatic lesions are caused by Listeria-elicited CD8(+) T cells secreting high levels of TNF-alpha that accumulate in the liver of Listeria-infected TCRdelta(-/-) mice. Using isolated populations of gammadelta T cells from wild-type and cytokine-deficient strains of mice to reconstitute TCRdelta(-/-) mice, the TCR variable gene 4 (Vgamma4)(+) subset of gammadelta T cells was shown to protect against liver injury. Hepatoprotection was dependent upon their ability to produce IL-10 after TCR-mediated interactions with Listeria-elicited macrophages and CD8(+) T cells. IL-10-producing Vgamma4(+) T cells also contribute to controlling CD8(+) T cell expansion and to regulating and reducing TNF-alpha secretion by activated CD8(+) T cells. This effect on TNF-alpha production was directly attributed to IL-10. These findings identify a novel mechanism by which pathogen-elicited CD8(+) T cells are regulated via interactions with, and activation of, IL-10-producing hepatoprotective gammadelta T cells.
Original languageEnglish
Pages (from-to)2274-2283
Number of pages10
JournalEuropean Journal of Immunology
Volume38
Issue number8
DOIs
Publication statusPublished - Aug 2008

Keywords

  • Animals
  • CD8-Positive T-Lymphocytes
  • Interleukin-10
  • Listeriosis
  • Liver
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell, gamma-delta
  • T-Lymphocyte Subsets
  • Tumor Necrosis Factor-alpha

Cite this