Innate immune functions of human gammadelta T cells.
gammadelta T cells expressing the Vgamma9Vdelta2 T cell receptor (TCR) account for 1-10% of CD3(+) peripheral blood T lymphocytes. Vgamma9Vdelta2 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 gammadelta T cells to produce proinflammatory cytokines, notably interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). In addition, human gammadelta T cells express certain Toll-like receptors (TLR) and directly respond to the corresponding ligands. We have demonstrated expression of TLR3 in Vgamma9Vdelta2 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 Vgamma9Vdelta2 T cells as a link between innate and adaptive immune responses.
Beetz
Susann
S
Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, Michaelisstrasse 5, D-24105 Kiel, Germany.
Wesch
Daniela
D
Marischen
Lothar
L
Welte
Stefan
S
Oberg
Hans-Heinrich
HH
Kabelitz
Dieter
D
D017252:CD3 Complex / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007109:Immunity; D008024:Ligands; D008213:Lymphocyte Activation; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D011070:Poly I-C / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry / Q000276:immunology*; D013729:Terpenes / Q000737:chemistry; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017252:CD3 Complex; D016207:Cytokines; D008024:Ligands; D016692:Receptors, Antigen, T-Cell, gamma-delta; C495344:TLR3 protein, human; D013729:Terpenes; D051196:Toll-Like Receptor 3; D014409:Tumor Necrosis Factor-alpha; D011070:Poly I-C