Gammadelta 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 gammadelta T-cell-deficient mice. We therefore asked whether gammadelta T cells have regulatory functions.


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.
Hoffmann
Jörg C
JC
Medizinische Klinik I, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. joerg.hoffmann@st-marienkrankenhaus.de
Pawlowski
Nina N
NN
Grollich
Katja
K
Loddenkemper
Christoph
C
Zeitz
Martin
M
Kühl
Anja A
AA
D000814:Aniline Compounds / Q000633:toxicity; D000818:Animals; D001565:Benzoates / Q000633:toxicity; D015704:CD4 Antigens / Q000276:immunology; D049109:Cell Proliferation; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007111:Immunity, Cellular; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
C501686:2,4,6-trinitroanilino benzoic acid; D000814:Aniline Compounds; D001565:Benzoates; D015704:CD4 Antigens; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit