Cutting Edge: TGF-β1 and IL-15 Induce FOXP3+ γδ Regulatory T Cells in the Presence of Antigen Stimulation

Several subsets of alpha beta regulatory T cells (Tregs) have been described and studied intensively, but the potential regulatory role of gamma delta T cells remains largely unclear. Lymphocytes expressing gamma delta TCR are involved in both innate and adaptive immune responses, and their major adult human peripheral blood subset (V gamma 9V delta 52) displays a broad reactivity against microbial agents and tumors. In this study we report that gamma delta T lymphocytes with regulatory functions (V delta 2 Tregs) are induced in vitro in the presence of specific Ag stimulation and cytokines (TGF-beta 1 and IL-15). These cells express FOXP3 and, similarly as alpha beta Tregs, suppress the proliferation of anti-CD3/anti-CD28 stimulated-PBMC. Phenotypic and functional analyses of V delta 2 Tregs will very likely improve our understanding about the role of gamma delta T cells in the pathogenesis of autoimmune, infectious, and neoplastic diseases. The Journal of Immunology, 2009, 183: 3574-3577.