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

Rhodes, Katherine A, Andrew, Elizabeth M, Newton, Darren J, Tramonti, Daniela and Carding, Simon R (2008) A subset of IL-10-producing gammadelta T cells protect the liver from Listeria-elicited, CD8(+) T cell-mediated injury. European Journal of Immunology, 38 (8). pp. 2274-2283. ISSN 0014-2980

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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.

Item Type:	Article
Uncontrolled 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
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User:	EPrints Services
Date Deposited:	25 Nov 2010 11:13
Last Modified:	12 Jan 2023 15:31
URI:	https://ueaeprints.uea.ac.uk/id/eprint/15086
DOI:	10.1002/eji.200838354

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