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

摘要

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 gammadelta T-cell-deficient mice. We therefore asked whether gammadelta T cells have regulatory functions. MATERIALS AND METHODS: gammadelta T cells were isolated from spleens and mesenteric lymph nodes of C57BL/6 wild-type (wt) mice. Proliferation and cytokine secretion of gammadelta T cells were quantified by [(3)H] thymidine incorporation and ELISA. Additionally, proliferation of carboxyfluorescein diacetate succinimidylester-labelled CD4(+) T cells cocultured with gammadelta T cells was analysed by flow cytometry. Finally, gammadelta 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: gammadelta 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 gammadelta 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-alpha and increased IL-10 and TGF-beta secretion from intestinal and splenic lymphocytes. CONCLUSIONS: Murine gammadelta 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 gammadelta T cells can be used for immunotherapy of human inflammatory bowel disease.