| TLR-activated dendritic cells enhance the response of aged naive CD4 T cells via an IL-6-dependent mechanism. | |
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MedLine Citation:
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PMID: 20980632 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The most effective immunological adjuvants contain microbial products, such as TLR agonists, which bind to conserved pathogen recognition receptors. These activate dendritic cells (DCs) to become highly effective APCs. We assessed whether TLR ligand-treated DCs can enhance the otherwise defective response of aged naive CD4 T cells. In vivo administration of CpG, polyinosinic-polycytidylic acid, and Pam(3)CSK(4) in combination with Ag resulted in the increased expression of costimulatory molecules and MHC class II by DCs, increased serum levels of the inflammatory cytokines IL-6 and RANTES, and increased cognate CD4 T cell responses in young and aged mice. We show that, in vitro, preactivation of DCs by TLR ligands makes them more efficient APCs for aged naive CD4 T cells. After T-DC interaction, there are enhanced production of inflammatory cytokines, particularly IL-6, and greater expansion of the aged T cells, resulting from increased proliferation and greater effector survival with increased levels of Bcl-2. TLR preactivation of both bone marrow-derived and ex vivo DCs improved responses. IL-6 produced by the activated DCs during cognate T cell interaction was necessary for enhanced aged CD4 T cell expansion and survival. These studies suggest that some age-associated immune defects may be overcome by targeted activation of APCs by TLR ligands. |
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Authors:
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Stephen C Jones; Vinayak Brahmakshatriya; Gail Huston; John Dibble; Susan L Swain |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-27 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-18 Completed Date: 2011-01-10 Revised Date: 2011-06-20 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 6783-94 Citation Subset: AIM; IM |
Affiliation:
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Trudeau Institute, Saranac Lake, NY 12983, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Antigen-Presenting Cells / cytology, immunology, metabolism CD4-Positive T-Lymphocytes / cytology*, immunology*, metabolism Cell Aging / immunology* Cell Communication / immunology Cell Proliferation Cell Survival / immunology Cells, Cultured Coculture Techniques Dendritic Cells / cytology, immunology*, metabolism* G0 Phase / immunology* Interleukin-6 / biosynthesis, physiology* Ligands Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Transgenic Molecular Sequence Data Toll-Like Receptors / agonists, metabolism, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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AG021600/AG/NIA NIH HHS; AG025805/AG/NIA NIH HHS; F32 AG027641/AG/NIA NIH HHS; R37 AG025805-08/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-6; 0/Ligands; 0/Toll-Like Receptors |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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