Donor-strain-derived immature dendritic cell pre-treatment induced hyporesponsiveness against allogeneic antigens
Donor-strain-derived immature dendritic cell pre-treatment induced hyporesponsiveness against allogeneic antigens
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DOI：
10.1111/j.1365-2567.2009.03158.x
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发表时间：
2010-04-01
期刊：
影响因子：
6.4
通讯作者：
Kim, Yon Su
中科院分区：
文献类型：
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作者：
Kang, Hee Gyung;Lee, Jung Eun;Kim, Yon Su
P>抗原呈递树突状细胞 (DC) 的成熟是免疫调节和整体免疫反应的重要决定因素。我们假设，用骨髓来源的供体菌株固定的未成熟树突状细胞（FIDC）对受体进行预处理，可以诱导对供体同种异体抗原的免疫反应降低并提高同种异体移植物的存活率。供体菌株来源的成熟和未成熟 DC 在移植前进行固定，以确保它们具有稳定的免疫原性表型。固定的成熟 DC 有效诱导受体中的同种异体 T 细胞增殖，而 FIDC 无法引发同种异体 T 细胞反应。先前暴露于 FIDC 的 T 细胞保持幼稚表型，并且在注射到经致死照射的供体品系小鼠后无法广泛分裂。用供体菌株 FIDC 对受体进行预处理可显着延长胰岛以及同种异体皮肤移植物的存活时间。然而，FIDC 注射引起的 T 细胞反应低下可通过耗竭 CD4+ CD25+ T 细胞而消除。因此，FIDC 诱导的 T 细胞反应低下可能反映的是无反应性，而不是特异性缺失。我们的研究结果表明，供体菌株的 FIDC 可用于诱导移植物长期存活。
P>The maturation of antigen-presenting dendritic cells (DCs) serves as an important determinant for the regulation of immunity, and overall immune response. We hypothesized that a reduced immune response to donor alloantigens and improved allograft survival could be induced by pre-treating recipients with bone-marrow-derived donor-strain fixed immature DCs (FIDCs). Donor-strain-derived mature and immature DCs were fixed before grafting to ensure that they possessed a stable immunogenic phenotype. The fixed mature DCs effectively induced allogeneic T-cell proliferation in recipients, whereas FIDCs were unable to elicit an allogeneic T-cell response. T cells that had previously been exposed to FIDCs maintained naive phenotypes and were unable to extensively divide after injection into lethally irradiated donor-strain mice. The pre-treatment of recipients with donor-strain FIDCs markedly prolonged the survival of islet as well as skin allografts. However, T-cell hyporesponsiveness induced by FIDC injection was abrogated by the depletion of CD4+ CD25+ T cells. Consequently, FIDC-induced T-cell hyporesponsiveness could reflect anergy rather than specific deletion. Our findings suggest that FIDCs of donor strain could be used to induce long-term graft survival.