TLR-activated dendritic cells enhance the response of aged naive CD4 T cells via an IL-6-dependent mechanism.
TLR-activated dendritic cells enhance the response of aged naive CD4 T cells via an IL-6-dependent mechanism.
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DOI：
10.4049/jimmunol.0901296
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发表时间：
2010-12-01
期刊：
影响因子：
--
通讯作者：
Swain SL
中科院分区：
文献类型：
--
作者：
Jones SC;Brahmakshatriya V;Huston G;Dibble J;Swain SL
最有效的免疫佐剂含有微生物产物，例如Toll样受体（TLR）激动剂，其结合保守的病原体相关识别受体。这些激活树突状细胞（DC）成为高效的抗原呈递细胞（APC）。我们评估了TLR配体处理的DC是否可以增强老年幼稚CD 4 T细胞的其他缺陷反应。CpG、PolyI：C和Pam 3CSK 4与抗原联合体内给药导致树突状细胞（DC）表达的共刺激分子和MHC II类分子增加，炎性细胞因子IL-6和RANTES的血清水平升高，以及年轻和老年小鼠中同源CD 4 T细胞应答增加。我们表明，在体外，TLR配体预活化DC使其更有效的APC老化的幼稚CD 4 T细胞。在T：DC相互作用之后，炎性细胞因子（特别是IL-6）的产生增强，并且老化T细胞的扩增更大，这是由于增殖增加和Bcl-2水平增加的效应子存活更大。TLR预活化骨髓来源的DC和离体DC均改善了应答。在同源T细胞相互作用期间由活化的DC产生的IL-6对于增强的老化CD 4 T细胞扩增和存活是必需的。这些研究表明，一些与年龄相关的免疫缺陷可以通过TLR配体靶向激活APC来克服。
The most effective immunological adjuvants contain microbial products, such as toll like receptor (TLR) agonists, which bind to conserved pathogen-associated recognition receptors. These activate dendritic cells (DC) to become highly effective antigen-presenting cells (APC). We assessed whether TLR ligand-treated DC can enhance the otherwise defective response of aged naïve CD4 T cells. In vivo administration of CpG, PolyI:C and Pam3CSK4 in combination with antigen resulted in the increased expression of costimulatory molecules and MHC class II by dendritic cells (DC), elevated 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, pre-activation of DC by TLR ligands makes them more efficient APC for aged naïve CD4 T cells. Following 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 pre-activation of both bone marrow derived and ex vivo DC improved responses. IL-6 produced by the activated DC 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 APC by TLR ligands.
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