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International Journal of Colorectal Disease

Published in:

01-10-2008 | Original Article

γδ T lymphocytes: a new type of regulatory T cells suppressing murine 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis

Authors: Jörg C. Hoffmann, Nina N. Pawlowski, Katja Grollich, Christoph Loddenkemper, Martin Zeitz, Anja A. Kühl

Published in: International Journal of Colorectal Disease | Issue 10/2008

Abstract

Background

The intestinal immune system is continuously challenged by antigen without becoming dysregulated. However, injury of the mucosa by, i.e. dextran sulphate sodium causes severe inflammation in γδ T-cell-deficient mice. We therefore asked whether γδ T cells have regulatory functions.

Materials and methods

γδ T cells were isolated from spleens and mesenteric lymph nodes of C57BL/6 wild-type (wt) mice. Proliferation and cytokine secretion of γδ T cells were quantified by [³H] thymidine incorporation and ELISA. Additionally, proliferation of carboxyfluorescein diacetate succinimidylester-labelled CD4⁺ T cells cocultured with γδ T cells was analysed by flow cytometry. Finally, γδ T cells from wt or interleukin-10 transgenic (IL-10tg) mice were transferred into congenic mice with 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis.

Results

γδ T cells were hyporesponsive to CD3/CD28 stimulation and suppressed CD4⁺ T-cell proliferation (up to 66 ± 7% suppression) in vitro. Further, the preventive transfer of wt or IL-10tg γδ T cells ameliorated TNBS-induced colitis resulting in prolonged survival and reduced histological damage (1.5 ± 0.4 and 1.3 ± 0.2, respectively vs. 3.8 ± 0.3 in untransferred mice, p < 0.05). This was accompanied by reduced TNF-α and increased IL-10 and TGF-β secretion from intestinal and splenic lymphocytes.

Conclusions

Murine γδ T cells are a new type of regulatory T cells in vitro and act protective on mouse TNBS-induced colitis in vivo. Future studies have to define the underlying mechanism and to investigate whether γδ T cells can be used for immunotherapy of human inflammatory bowel disease.

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Title: γδ T lymphocytes: a new type of regulatory T cells suppressing murine 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis
Authors: Jörg C. Hoffmann
Nina N. Pawlowski
Katja Grollich
Christoph Loddenkemper
Martin Zeitz
Anja A. Kühl
Publication date: 01-10-2008
Publisher: Springer-Verlag
Published in: International Journal of Colorectal Disease / Issue 10/2008
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-008-0535-8

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γδ T lymphocytes: a new type of regulatory T cells suppressing murine 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis

Abstract

Background

Materials and methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

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Abstract

Background

Materials and methods

Results

Conclusions

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