Innate immune functions of human γδ T cells

gamma delta T cells expressing the V gamma 9V delta 2 T cell receptor (TCR) account for 1-10% of CD3(+) peripheral blood T lymphocytes. V gamma 9V delta 2 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 isoprenold biosynthesis. Such phosphoantigens rapidly and selectively activate human gamma delta T cells to produce proinflammatory cytokines, notably interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). In addition, human gamma delta T cells express certain Toll-like receptors (TLR) and directly respond to the corresponding ligands. We have demonstrated expression of TLR3 in V gamma 9V delta 2 T cells and striking costimulatory effects of the ligand polyinosinic-polycytidylic acid (polyI:C) on TCR-stimulated IFN-gamma 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 V gamma 9V delta 2 T cells as a link between innate and adaptive immune responses. (C) 2007 Elsevier GmbH. All rights reserved.