Double stranded RNA- relative to other TLR ligand-activated dendritic cells induce extremely polarized human Th1 responses

被引:21
作者
Benwell, Risa K. [1 ]
Hruska, Jennifer E. [1 ]
Fritsche, Kevin L. [2 ]
Lee, David R. [1 ]
机构
[1] Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Columbia, MO 65212 USA
[2] Univ Missouri, Dept Nutr Sci, Div Anim Sci, Coll Agr Food & Nat Resources, Columbia, MO 65212 USA
关键词
Human; Dendritic cell; Toll-like receptor; CD4(+) T cell differentiation; HELPER PHENOTYPE DEVELOPMENT; T-CELLS; RECEPTOR AGONISTS; CUTTING EDGE; AUTOIMMUNE INFLAMMATION; HUMAN BLOOD; IN-VITRO; CPG-DNA; IL-23; IL-12;
D O I
10.1016/j.cellimm.2010.05.008
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
To better understand the relative efficiencies of using different TLR ligand-activated DCs to induce human CD4(+) T lymphocyte responses, human DCs were activated with two viral and two bacterial TLR ligands, and Melt production of IL12. TNF alpha, and IL10 was examined While the two viral TLR ligands (ssRNA and dsRNA) induced DC production of detectable levels of IL12p70, DCs activated by the two bacterial TLR ligands (LPS and flagellin) induced increased proliferation of human allogeneic naive CD4(+) T cells dsRNA-activated DCs induced increased Th1 and decreased Th2 differentiation, resulting in extremely polarized responses relative to those induced by unstimulated and other TLR ligand-activated DCs Neutralization of IL12p70 abrogated most of the Th1 skewing induced by all TLR ligand-activated moDCs Collectively, these results demonstrate that dsRNA-activated DCs induce more highly polarized human Th1 responses than the other TLR ligand-activated DCs tested here These results have implications for TLR ligands in immunotherapy. (C) 2010 Elsevier Inc All rights reserved
引用
收藏
页码:119 / 126
页数:8
相关论文
共 46 条
[1]
Cutting edge: Different toll-like receptor agonists instruct dendritic cells to induce distinct th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-fos [J].
Agrawal, S ;
Agrawal, A ;
Doughty, B ;
Gerwitz, A ;
Blenis, J ;
Van Dyke, T ;
Pulendran, B .
JOURNAL OF IMMUNOLOGY, 2003, 171 (10) :4984-4989
[2]
Toll-like receptor signalling [J].
Akira, S ;
Takeda, K .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (07) :499-511
[3]
Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3 [J].
Alexopoulou, L ;
Holt, AC ;
Medzhitov, R ;
Flavell, RA .
NATURE, 2001, 413 (6857) :732-738
[4]
Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells [J].
Amsen, D ;
Blander, JM ;
Lee, GR ;
Tanigaki, K ;
Honjo, T ;
Flavell, RA .
CELL, 2004, 117 (04) :515-526
[5]
Toll-like receptor (TLR)-3, but not TLR4, agonist protects against genital herpes infection in the absence of inflammation seen with CpG DNA [J].
Ashkar, AA ;
Yao, XD ;
Gill, N ;
Sajic, D ;
Patrick, AJ ;
Rosenthal, KL ;
Rosenthal, L .
JOURNAL OF INFECTIOUS DISEASES, 2004, 190 (10) :1841-1849
[6]
Asselin S, 1998, EUR J IMMUNOL, V28, P532, DOI 10.1002/(SICI)1521-4141(199802)28:02<532::AID-IMMU532>3.0.CO
[7]
2-U
[8]
Bauer S, 2002, CURR TOP MICROBIOL, V270, P145
[9]
Improved methods for the generation of dendritic cells from nonproliferating progenitors in human blood [J].
Bender, A ;
Sapp, M ;
Schuler, G ;
Steinman, RM ;
Bhardwaj, N .
JOURNAL OF IMMUNOLOGICAL METHODS, 1996, 196 (02) :121-135
[10]
Essential and synergistic roles of IL1 and IL6 in human Th17 differentiation directed by TLR ligand-activated dendritic cells [J].
Benwell, Risa K. ;
Lee, David R. .
CLINICAL IMMUNOLOGY, 2010, 134 (02) :178-187