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Published on: September 1, 2015
Polyinosinic-polycytidylic acid-mediated stimulation of human gammadelta T cells via CD11c dendritic cell-derived
Volker Kunzmann1, Eva Kretzschmar, Thomas Herrmann
1Medizinische Poliklinik, University of Würzburg, Würzburg, Germany. kunzmann_v@klinik.uni-wuerzburg.de
Abstract:
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.
Insights
Polyinosinic-polycytidylic acid (poly(I:C)), a mimic of viral double-stranded RNA, activates gammadelta T cells indirectly. This activation relies on type I interferons produced by dendritic cells expressing Toll-like receptor 3.
Area of Science:
- Immunology
- Innate Immunity
- T-cell Biology
Background:
- Pathogen-associated molecular patterns (PAMPs) are crucial for innate immune responses.
- Double-stranded RNA (dsRNA), mimicked by polyinosinic-polycytidylic acid (poly(I:C)), is a key viral PAMP.
- gammadelta T cells play a role in immune surveillance and early responses.
Purpose of the Study:
- To investigate the costimulatory capacity of poly(I:C) on gammadelta T cells.
- To elucidate the mechanism of poly(I:C)-mediated gammadelta T cell activation.
- To determine the role of dendritic cells and cytokines in this process.
Main Methods:
- Stimulation of peripheral blood mononuclear cells with poly(I:C).
- Analysis of gammadelta T cell activation markers (CD69) and proliferation.
- Depletion of CD11c(+) dendritic cells and use of neutralizing antibodies.
- Assessment of cytokine involvement (Type I IFNs, IL-15).
Main Results:
- Poly(I:C) demonstrated potent costimulatory capacity for gammadelta T cells.
- Poly(I:C) induced CD69 expression and enhanced proliferation of gammadelta T cells.
- Activation was indirect, mediated by CD11c(+) dendritic cells expressing TLR3.
- Type I interferons, but not IL-15, were identified as key mediators.
Conclusions:
- Poly(I:C)-induced gammadelta T cell activation is indirectly mediated by type I IFNs from TLR3+ dendritic cells.
- This pathway highlights a rapid mechanism for gammadelta T cell activation during viral infections.
- gammadelta T cells may contribute significantly to early antiviral immunity.
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