Direct costimulatory effect of TLR3 ligand poly(I:C) on human gamma delta T lymphocytes.
TLR3 recognizes viral dsRNA and its synthetic mimetic polyinosinic-polycytidylic acid (poly(I:C)). TLR3 expression is commonly considered to be restricted to dendritic cells, NK cells, and fibroblasts. In this study we report that human gammadelta and alphabeta T lymphocytes also express TLR3, as shown by quantitative real-time PCR, flow cytometry, and confocal microscopy. Although T cells did not respond directly to poly(I:C), we observed a dramatic increase in IFN-gamma secretion and an up-regulation of CD69 when freshly isolated gammadelta T cells were stimulated via TCR in the presence of poly(I:C) without APC. IFN-gamma secretion was partially inhibited by anti-TLR3 Abs. In contrast, poly(I:C) did not costimulate IFN-gamma secretion by alphabeta T cells. These results indicate that TLR3 signaling is differentially regulated in TCR-stimulated gammadelta and alphabeta T cells, suggesting an early activation of gammadelta T cells in antiviral immunity.
Wesch
Daniela
D
Institute of Immunology, Universitätsklinikum Schleswig-Holstein Campus Kiel, Kiel, Germany. wesch@immunologie.uni-kiel.de
Beetz
Susann
S
Oberg
Hans-Heinrich
HH
Marget
Matthias
M
Krengel
Kirsten
K
Kabelitz
Dieter
D
D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D006801:Humans; D007369:Interferon Inducers / Q000378:metabolism / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D011070:Poly I-C / Q000378:metabolism / Q000494:pharmacology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis / Q000378:metabolism*
D007369:Interferon Inducers; D008024:Ligands; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D007371:Interferon-gamma; D011070:Poly I-C