The adjuvant effects of the toll-like receptor 3 ligand polyinosinic-cytidylic acid poly (I:C) on antigen-specific CD8+ T cell responses are partially dependent on NK cells with the induction of a beneficial cytokine milieu
| Autor: | Mohamed L. Salem, Sabry A. El-Naggar, Andre N. Kadima, David J. Cole, William E. Gillanders |
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| Rok vydání: | 2005 |
| Předmět: |
Time Factors
medicine.medical_treatment T cell Biology CD8-Positive T-Lymphocytes Natural killer cell Proinflammatory cytokine Interleukin 21 Mice Adjuvants Immunologic medicine Cytotoxic T cell Animals Mice Inbred BALB C General Veterinary General Immunology and Microbiology Macrophages Vaccination Public Health Environmental and Occupational Health Dendritic cell Molecular biology Toll-Like Receptor 3 Killer Cells Natural Mice Inbred C57BL Infectious Diseases medicine.anatomical_structure Cytokine Poly I-C Immunology Interferon Type I Molecular Medicine Cytokines Chemokines Peptides CD8 |
| Zdroj: | Vaccine. 24(24) |
| ISSN: | 0264-410X |
| Popis: | Poly (I:C), a TLR3 ligand, has shown promise as a vaccine adjuvant to CD8(+) T cell responses. The underlying mechanisms involved in creating this adjuvant response in vivo, however, have not been well defined. In this study, we explored the contribution of NK cells and inflammatory cytokines in mediation the poly (I:C) adjuvant effects. Enhanced antigen-specific CD8(+) T cell responses were observed only when poly (I:C) was administered within 4h of peptide vaccination. Poly (I:C) treatment was associated with a rapid induction of inflammatory cytokines in the serum, including IL-6, IL-10, MCP-1, TNF-alpha, IFN-alpha, and IFN-gamma, and selective increases in the numbers of NK (NK1.1(+)CD11b(+)) cells and Mvarphi (NK1.1(-)CD11b(+)), but not NK T (CD3(+)NK1.1(+)) cells. NK cells were required for the adjuvant effects of poly (I:C). Poly (I:C) treatment in TNF-alpha, type I IFNR, IFN-gamma, IL-6, IL-12Rbeta2, or IL-15 gene-deficient mice revealed a reciprocal interaction and interdependence in the induction of these cytokines, where the absence of one cytokine impacted on the production of others. Further, the adjuvant effects of poly (I:C) were dependent on the endogenous levels of type I IFNs, TNF-alpha, IFN-gamma, IL-12, and IL-15. IFN-alpha and IFN-beta, but not TNF-alpha or IL-6, were able to mimic the adjuvant effects of poly (I:C). We conclude that the adjuvant effects of poly (I:C) on antigen-specific CD8(+) T cells appeared to be exquisitely dependent on the rapid induction of certain beneficial cytokines produced in part by NK cells. |
| Databáze: | OpenAIRE |
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