Effect of aging on bone marrow-derived murine CD11c+CD4-CD8α- dendritic cell function
Effect of aging on bone marrow-derived murine CD11c+CD4-CD8α- dendritic cell function
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DOI：
10.1093/gerona/61.10.1039
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发表时间：
2006-10-01
影响因子：
5.1
通讯作者：
Yung, Raymond L.
中科院分区：
文献类型：
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作者：
Grolleau-Julius, Annabelle;Garg, Monika R.;Yung, Raymond L.
树突状细胞（Dendritic cells，DCs）是肿瘤免疫治疗中常用的细胞佐剂。然而，尽管DC免疫疗法主要针对老年人群，但对衰老对DC功能的影响知之甚少。在这里，我们比较了老年和年轻C57 BL/6小鼠骨髓来源的CD 11 c（+）CD 4（-）CD 80 α（-）DC的T细胞刺激，细胞因子产生和肿瘤监视功能。在刺激同基因CD 4 + T细胞增殖方面，老年未成熟骨髓来源的CD 4-CD 8 α-DCs（imDCs）的有效性比年轻DCs低4倍。与年轻DC相比，老年imDC还具有降低的DC特异性/细胞内粘附分子3型抓取非整合素（DC-SIGN）表达。有趣的是，用卵清蛋白肽脉冲的年轻DC处理的小鼠比用卵清蛋白肽脉冲的老年DC处理的小鼠表现出显著更大的肿瘤消退。老终末分化的骨髓来源的DC（tDC）也具有增加的白细胞介素-10，但减少的白细胞介素-6和肿瘤坏死因子-a的产生。总之，这些结果对基于DC的肿瘤免疫治疗在老年人中的临床应用具有重要意义。
Dendritic cells (DCs) are actively used as cellular adjuvant in cancer immunotherapy. However, although DC immunotherapies primarily target the elderly population, little is known about the effect of aging on DC functions. Here, we compared the T-cell stimulation, cytokine production, and tumor surveillance functions of bone marrow-derived CD11c(+)CD4(-)CD80 alpha(-) DCs of old and young C57BL/6 mice. Old immature bone marrow-derived CD4(-)CD8 alpha(-) DCs (imDCs) were 4 times less effective than were young DCs in stimulating syngeneic CD4(+) T-cell proliferation. Old imDCs also have decreased DC-specific/intracellular adhesion molecule type 3-grabbing, nonintegrin (DC-SIGN) expression compared to young DCs. Interestingly, mice treated with the ovalbumin peptide-pulsed young DCs exhibited significantly greater tumor regression than with ovalbumin peptide-pulsed old DCs. Old terminally differentiated bone marrow-derived DCs (tDC) also have increased interleukin-10, but decreased interleukin-6 and tumor necrosis factor-a production. Taken together, these results have important implications in the clinical application of DC-based tumor immunotherapy in elderly persons.