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Polyinosinic‐polycytidylic acid‐mediated stimulation of human γδ T cells via CD11c + dendritic cell‐derived type I interferons
Author(s) -
Kunzmann Volker,
Kretzschmar Eva,
Herrmann Thomas,
Wilhelm Martin
Publication year - 2004
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2004.01908.x
Subject(s) - stimulation , cd11c , microbiology and biotechnology , chemistry , cell type , interferon , cell , biology , biochemistry , virology , neuroscience , phenotype , gene
Summary 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 γδ T‐cell costimulatory capacity. Within peripheral blood mononuclear cells, poly(I:C)‐stimulated γδ 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‐α, IFN‐β) and interleukin‐15 (IL‐15) showed a similar activation pattern of γδ T cells. γδ T‐cell clones and purified γδ 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 γδ 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 γδ T cells. Experiments with neutralizing antibodies indicated that type I IFNs, but not IL‐15, contributed to the poly(I:C)‐mediated activation of γδ T cells. In conclusion, γδ 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, γδ T cells can be rapidly activated by type I interferons and may contribute to effective antiviral responses.