Daily subcutaneous injections of peptide induce CD4+ CD25+ T regulatory cells.
Daily subcutaneous injections of peptide induce CD4+ CD25+ T regulatory cells.
复制标题
每日皮下注射肽可诱导 CD4 CD25 T 调节细胞。
DOI：
10.1111/j.1365-2249.2007.03402.x
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发表时间：
2007
影响因子：
4.6
通讯作者：
Seroogy,CM
中科院分区：
文献类型：
--
作者：
Dahlberg,PE;Schartner,JM;Timmel,A;Seroogy,CM
人们正在探索多肽免疫疗法来调节各种疾病状态，然而，其作用机制仍然知之甚少。在这项研究中，我们研究了皮下多肽免疫程序诱导CD4+CD25+T调节细胞的能力。将DO11·10T细胞受体转基因小鼠(RAG2-/-)皮下注射不同剂量的精制卵白蛋白多肽，连续16 d。虽然这些小鼠没有CD4+CD25+T调节细胞，但按照这种注射程序，发现高达30%的CD4+细胞表达CD25。实时定量聚合酶链式反应(QPCR)分析显示诱导的CD4+CD25+T细胞叉头盒P3(FoxP3)表达增加，提示这些细胞可能具有调节功能。玻璃化诱导的CD4+CD25+T细胞的增殖和抑制分析显示，除了强大的抑制能力外，还具有深刻的无能表型。重要的是，将诱导的CD4+CD25+T细胞和5，6-羧基琥珀酰亚胺基荧光酯(CFSE)标记的初始CD4+T细胞(应答细胞)共同注射到BALB/c受体小鼠中，减少了应答细胞的增殖和分化，以应对OVA323-339肽加佐剂的攻击。我们的结论是，反复皮下注射低剂量多肽可诱导出具有潜在体外抑制能力的CD4+CD25+FoxP3+T调节细胞，从而提示多肽免疫治疗的机制之一可能是诱导CD4+CD25+FoxP3+T调节细胞。
Peptide immunotherapy is being explored to modulate varied disease states; however, the mechanism of action remains poorly understood. In this study, we investigated the ability of a subcutaneous peptide immunization schedule to induce of CD4+CD25+T regulatory cells. DO11·10 T cell receptor (TCR) transgenic mice on a Rag 2–/–background were injected subcutaneously with varied doses of purified ovalbumin (OVA323–339) peptide daily for 16 days. While these mice have no CD4+CD25+T regulatory cells, following this injection schedule up to 30% of the CD4+cells were found to express CD25. Real-time quantitative polymerase chain reaction (QPCR) analysis of the induced CD4+CD25+T cells revealed increased expression of forkhead box P3 (FoxP3), suggesting that these cells may have a regulatory function. Proliferation and suppression assaysin vitroutilizing the induced CD4+CD25+T cells revealed a profound anergic phenotype in addition to potent suppressive capability. Importantly, co-injection of the induced CD4+CD25+T cells with 5,6-carboxy-succinimidyl-fluorescence-ester (CFSE)-labelled naive CD4+T cells (responder cells) into BALB/c recipient mice reduced proliferation and differentiation of the responder cells in response to challenge with OVA323–339peptide plus adjuvant. We conclude that repeated subcutaneous exposure to low-dose peptide leads tode novoinduction of CD4+CD25+FoxP3+T regulatory cells with potentin vitroandin vivosuppressive capability, thereby suggesting that one mechanism of peptide immunotherapy appears to be induction of CD4+CD25+Foxp3+T regulatory cells.