Polyinosinic-polycytidylic acid-mediated stimulation of human gammadelta T cells via CD11c dendritic cell-derived type I interferons.
The recognition of pathogen-associated molecular patterns (PAMPs) by the innate immune system is a crucial step in inducing effective immune responses. Double-stranded RNA [mimicked by polyinosinic-polycytidylic acid (poly(I:C)], synthesized by various types of viruses, represents one important member of these immunostimulatory microbial components. Here we report that poly(I:C) has potent gammadelta T-cell costimulatory capacity. Within peripheral blood mononuclear cells, poly(I:C)-stimulated gammadelta T cells expressed increased levels of CD69 and exhibited significantly enhanced antigen-mediated proliferation in response to isopentenylpyrophosphate (IPP). Among several recombinant cytokines tested, type I interferons (IFN-alpha, IFN-beta) and interleukin-15 (IL-15) showed a similar activation pattern of gammadelta T cells. gammadelta T-cell clones and purified gammadelta T cells did not respond to poly(I:C), indicating indirect effects of this compound. Depletion of CD11c(+) dendritic cells (DC), which express Toll-like receptor 3 (TLR3), known to recognize poly(I:C), abrogated poly(I:C)-mediated stimulation of gammadelta T cells. In addition, the supernatant of poly(I:C)-treated CD11c(+) DC was able to mimic the stimulatory effects of poly(I:C) on gammadelta T cells. Experiments with neutralizing antibodies indicated that type I IFNs, but not IL-15, contributed to the poly(I:C)-mediated activation of gammadelta T cells. In conclusion, gammadelta T-cell activation by immunostimulatory double-stranded RNA, such as poly(I:C), is indirectly mediated via type I IFNs derived from TLR3-expressing CD11c(+) DCs. These results suggest that upon confrontation with certain viruses, gammadelta T cells can be rapidly activated by type I interferons and may contribute to effective antiviral responses.
Kunzmann
Volker
V
Medizinische Poliklinik, University of Würzburg, Würzburg, Germany. kunzmann_v@klinik.uni-wuerzburg.de
Kretzschmar
Eva
E
Herrmann
Thomas
T
Wilhelm
Martin
M
D000485:Allergens / Q000276:immunology*; D000998:Antiviral Agents / Q000494:pharmacology*; D039521:CD11c Antigen / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors
D000485:Allergens; D000998:Antiviral Agents; D039521:CD11c Antigen; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D007371:Interferon-gamma; D011070:Poly I-C