Generation of Human Regulatory γδ T Cells by TCRγδ Stimulation in the Presence of TGF-β and Their Involvement in the Pathogenesis of Systemic Lupus Erythematosus

As a component of the innate immune cell population, gamma delta T cells are involved in tumor immunosurveillance and host defense against viral invasion. In this study, we demonstrated a novel function of human gamma delta T cells as regulatory cells by detecting their suppressive effect on the proliferation of autologous naive CD4(+) T cells. These regulatory gamma delta T cells (gamma delta Tregs) could be generated in vitro by stimulating with anti-TCR gamma delta in the presence of TGF-beta and IL-2. Similar to CD4(+)Foxp3(+) Tregs, gamma delta Tregs also expressed Foxp3. Additionally, they primarily belonged to the V delta 1 subset with a CD27(+)CD25(high) phenotype. Furthermore, these gamma delta Tregs showed an immunoregulatory activity mainly through cell-to-cell contact. Importantly, this gamma delta regulatory population decreased in the peripheral blood of systemic lupus erythematosus patients, suggesting a potential mechanism in understanding the pathogenesis of systemic lupus erythematosus. The Journal of Immunology, 2011, 186: 6693-6700.