Evans Tristan I, Reeves R Keith
Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, USA.
Clin Vaccine Immunol. 2013 Oct;20(10):1642-6. doi: 10.1128/CVI.00419-13. Epub 2013 Aug 21.
Tissue-directed trafficking of dendritic cells (DCs) as natural adjuvants and/or direct vaccine carriers is highly attractive for the next generation of vaccines and immunotherapeutics. Since these types of studies would undoubtedly be first conducted using nonhuman primate models, we evaluated the ability of all-trans-retinoic acid (ATRA) to induce gut-homing α4β7 expression on rhesus macaque plasmacytoid and myeloid DCs (pDCs and mDCs, respectively). Induction of α4β7 occurred in both a time-dependent and a dose-dependent manner with up to 8-fold increases for mDCs and 2-fold increases for pDCs compared to medium controls. ATRA treatment was also specific in inducing α4β7 expression, but not expression of another mucosal trafficking receptor, CCR9. Unexpectedly, upregulation of α4β7 was associated with a concomitant downregulation of CD62L, a marker of lymph node homing, indicating an overall shift in the trafficking repertoire. These same phenomena occurred with ATRA treatment of human and chimpanzee DCs, suggesting a conserved mechanism among primates. Collectively, these data serve as a first evaluation for ex vivo modification of primate DC homing patterns that could later be used in reinfusion studies for the purposes of immunotherapeutics or mucosa-directed vaccines.
将树突状细胞（DCs）作为天然佐剂和/或直接疫苗载体进行组织定向运输，对下一代疫苗和免疫疗法极具吸引力。由于这类研究无疑会首先在非人类灵长类动物模型上开展，我们评估了全反式维甲酸（ATRA）诱导恒河猴浆细胞样树突状细胞和髓样树突状细胞（分别为pDCs和mDCs）表达归巢至肠道的α4β7的能力。与培养基对照相比，α4β7的诱导呈时间依赖性和剂量依赖性，mDCs诱导增加高达8倍，pDCs诱导增加2倍。ATRA处理在诱导α4β7表达方面也具有特异性，但不诱导另一种黏膜运输受体CCR9的表达。出乎意料的是，α4β7的上调与淋巴结归巢标志物CD62L的下调同时出现，表明运输模式发生了总体转变。用ATRA处理人类和黑猩猩DCs时也出现了同样的现象,这表明灵长类动物中存在保守机制。总体而言,这些数据是对灵长类DC归巢模式进行离体修饰的首次评估，这种修饰随后可用于免疫治疗或黏膜定向疫苗的回输研究。
