Human peripheral γδ T cells possess regulatory potential

Deficiency in γδ T cells aggravates colitis in animal models suggesting that γδ T cells have regulatory properties. Therefore, proliferation, suppression and cytokine secretion of human γδ T cells were determined in vitro. Human peripheral γδ 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-γ (IFN-γ), interleukin-2 (IL-2), transforming growth factor-β (TGF-β) and IL-10 concentrations were measured by enzyme-linked immunosorbent assay; TGF-β messenger RNA was also measured by reverse transcription-polymerase chain reaction. The expression of latency associated peptide (LAP), a TGF-β complex component, intracellular cytokine content and T helper cell proliferation were measured by flow cytometry. Human γδ T cells showed poor proliferation upon CD3-CD28 stimulation and suppressed T helper cell growth stronger than CD4⁺ CD25⁺ T cells, although γδ T cells were FOXP3 negative. They secreted little IL-2 but high concentrations of IFN-γ, IL-10 and TGF-β. When looking at LAP expression the Vδ1 subset was found to be the main TGF-β producer compared to Vδ2 T cells. Taken together, peripheral γδ 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-β secretion, particularly by the Vδ1 subset.