Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs
Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs
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DOI：
10.1182/blood-2009-11-251231
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发表时间：
2010-06-03
期刊：
影响因子：
20.3
通讯作者：
Houghton, Alan N.
中科院分区：
文献类型：
--
作者：
Nakahara, Takeshi;Uchi, Hiroshi;Houghton, Alan N.
环磷酰胺（CTX）是一种常用的化疗药物，可增强免疫反应。已经描述了CTX促进效应T细胞的增殖和消除调节性T细胞（TCFs）的功能的能力。在这项研究中，我们研究了环磷酰胺治疗对树突状细胞（DC）亚群的影响，以及随后的结果对效应和抑制武器的适应性免疫。在次级淋巴组织中，组织来源的迁移性DC（迁移性DC）、淋巴组织驻留DC（驻留DC）和浆细胞样DC（pDC）被充分描述。CTX对CD 8（+）驻留DC具有显著的选择性细胞毒作用，但对皮肤来源的淋巴结（LN）和脾脏中的迁移DC或pDC无明显作用，导致这些DC亚群之间的失衡。CTX处理增加了DC在抗原呈递和细胞因子分泌中的效力，并部分抑制了TcR的抑制活性。CD 8（+）DCs的连续性转移可以在局部引流淋巴结中重建这一群体，并消除体内CTX的免疫增强作用。这些发现表明，CTX可能通过优先消耗CD 8（+）淋巴驻留DC来改善免疫应答，这导致体内Treg抑制减少和效应T细胞功能增强。（血。2010; 115（22）：4384-4392）
Cyclophosphamide (CTX), a commonly used chemotherapeutic agent can enhance immune responses. The ability of CTX to promote the proliferation of effector T cells and abrogate the function of regulatory T cells (Tregs) has been described. In this study, we examined the effects of CTX treatment on dendritic cell (DC) subsets and the subsequent outcome on the effector and suppressive arms of adaptive immunity. In secondary lymphoid tissues, tissue-derived migratory DCs (migratory DCs), lymphoid tissue resident DCs (resident DCs), and plasmacytoid DCs (pDCs) are well described. CTX has profound and selective cytotoxic effects on CD8(+) resident DCs, but not skin-derived migratory DCs or pDCs in lymph nodes (LNs) and spleen, causing an imbalance among these DC subsets. CTX treatment increases the potency of DCs in antigen presentation and cytokine secretion, and partially inhibits the suppressor activity of Tregs. Adoptive transfer of CD8(+) DCs can reconstitute this population in regional draining LNs and abrogate the immune-enhancing effects of CTX in vivo. These findings demonstrate that CTX may improve immune responses by preferentially depleting CD8(+) lymphoid-resident DCs, which leads to diminished Treg suppression and enhanced effector T-cell function in vivo. (Blood. 2010; 115(22): 4384-4392)