Innate immune functions of human γδ T cells

γδ T cells expressing the Vγ9Vδ2 T cell receptor (TCR) account for 1–10% of CD3+ peripheral blood T lymphocytes. Vγ9Vδ2 T cells use their TCR as a pattern recognition receptor to sense the presence of infection through specific recognition of intermediates of the microbial non-mevalonate pathway of isoprenoid biosynthesis. Such phosphoantigens rapidly and selectively activate human γδ T cells to produce proinflammatory cytokines, notably interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). In addition, human γδ T cells express certain Toll-like receptors (TLR) and directly respond to the corresponding ligands. We have demonstrated expression of TLR3 in Vγ9Vδ2 T cells and striking costimulatory effects of the ligand polyinosinic–polycytidylic acid (polyI:C) on TCR-stimulated IFN-γ production. Gene expression studies by microarray analysis identified additional genes that were up-regulated by combined TCR- and TLR3 stimulation. We discuss these findings in the context of the suspected role of human Vγ9Vδ2 T cells as a link between innate and adaptive immune responses.