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

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 gamma delta T-cell-deficient mice. We therefore asked whether gamma delta T cells have regulatory functions. Materials and methods gamma delta T cells were isolated from spleens and mesenteric lymph nodes of C57BL/6 wild-type (wt) mice. Proliferation and cytokine secretion of gamma delta T cells were quantified by [(3)H] thymidine incorporation and ELISA. Additionally, proliferation of carboxyfluorescein diacetate succinimidylester-labelled CD4(+) T cells cocultured with gamma delta T cells was analysed by flow cytometry. Finally, gamma delta 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 gamma delta 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 gamma delta 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 gamma delta 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 gamma delta T cells can be used for immunotherapy of human inflammatory bowel disease.