Human peripheral gammadelta T cells possess regulatory potential.

Deficiency in gammadelta T cells aggravates colitis in animal models suggesting that gammadelta T cells have regulatory properties. Therefore, proliferation, suppression and cytokine secretion of human gammadelta T cells were determined in vitro. Human peripheral gammadelta T cells were isolated from the whole blood of healthy donors by magnetic antibody cell sorting technology. The proliferation after CD3/CD28 stimulation was measured by (3)[H]thymidine incorporation. Interferon-gamma (IFN-gamma), interleukin-2 (IL-2), transforming growth factor-beta (TGF-beta) and IL-10 concentrations were measured by enzyme-linked immunosorbent assay; TGF-beta messenger RNA was also measured by reverse transcription-polymerase chain reaction. The expression of latency associated peptide (LAP), a TGF-beta complex component, intracellular cytokine content and T helper cell proliferation were measured by flow cytometry. Human gammadelta T cells showed poor proliferation upon CD3/CD28 stimulation and suppressed T helper cell growth stronger than CD4(+) CD25(+) T cells, although gammadelta T cells were FOXP3 negative. They secreted little IL-2 but high concentrations of IFN-gamma, IL-10 and TGF-beta. When looking at LAP expression the Vdelta1 subset was found to be the main TGF-beta producer compared to Vdelta2 T cells. Taken together, peripheral gammadelta T cells have in vitro a more potent regulatory potential than CD4(+) CD25(+) cells regarding T helper cell suppression. This is most likely the result of strong TGF-beta secretion, particularly by the Vdelta1 subset.