Alteration of the migratory behavior of UV-induced regulatory T cells by tissue-specific dendritic cells
Alteration of the migratory behavior of UV-induced regulatory T cells by tissue-specific dendritic cells
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DOI：
10.4049/jimmunol.178.2.877
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发表时间：
2007-01-15
影响因子：
4.4
通讯作者：
Schwarz, Thomas
中科院分区：
文献类型：
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作者：
Schwarz, Agatha;Maeda, Akira;Schwarz, Thomas
静脉注射时，紫外线辐射诱导的调节性 T 细胞 (UV-Treg) 会抑制致敏作用，但不会引起接触性超敏反应。因为 UV-Treg 表达淋巴结归巢受体 CD62 配体，静脉注射后注射后，它们迁移到淋巴结中，但不迁移到外周，因此抑制致敏，但不抑制诱发。我们试图改变 UV-Treg 的迁移行为，目的是让它们进入外周，从而抑制免疫反应的效应阶段。由于效应 T 细胞的组织选择性归巢是由组织特异性树突状细胞 (DC) 决定的，因此我们尝试通过 DC 重新编程 UV-Treg 的迁移行为。 2,4-二硝基氟苯烯 (DNFB) 特异性 UV-Treg 与表皮朗格汉斯细胞 (LC) 共孵育可阻断静脉注射时的诱导。注射到 DNFB 致敏小鼠体内。相反，静脉注射。注射未与 LC 一起孵育的 UV-Treg 不会抑制耳朵攻击。对于与来自骨髓、脾脏或淋巴结的 DC 共孵育的 UV-Treg 也观察到了相同的负面影响。通过不同 DC 类型的 MHC II 类表达检查，这种效应并非由于不同的成熟阶段所致。与 LC 一起孵育，而不是与骨髓来源的 DC 一起孵育，会下调 UV-Treg 上 CD62 配体的表达。因此，在静脉注射时，在耳朵中发现了与 LC 共孵育的 CFDA-SE 标记的 UV-Treg，但在淋巴结中没有发现。注射。这一发现表明，迁移行为可以被组织特异性 DC 重新编程，并且可能对尝试使用 Treg 来预防和治疗免疫介导的疾病的策略有所帮助。
UV radiation-induced regulatory T cells (UV-Treg) inhibit the sensitization but not the elicitation of contact hypersensitivity when injected i.v. Because UV-Treg express the lymph node homing receptor CD62 ligand, upon i.v. injection they migrate into the lymph nodes but not into the periphery and therefore inhibit sensitization but not elicitation. We tried to modify the migratory behavior of UV-Treg with the aim to get them into the periphery and thereby to suppress the effector phase of immune reactions. Because the tissue selective homing of T effector cells is determined by tissue-specific dendritic cells (DC), we attempted to reprogram the migratory behavior of UV-Treg by DC. 2,4-Dinitrofluorobencene (DNFB)-specific UV-Treg coincubated with epidermal Langerhans cells (LC) blocked the elicitation upon i.v. injection into DNFB-sensitized mice. In contrast, i.v. injection of UV-Treg not incubated with LC did not inhibit the ear challenge. The same negative effect was observed for UV-Treg coincubated with DC from bone marrow, spleen, or lymph nodes. This effect was not due to different maturation stages as checked by MHC class II expression of the different DC types. Incubation with LC but not with bone marrow-derived DC down-regulated the expression of CD62 ligand on UV-Treg. Accordingly, CFDA-SE labeled UV-Treg coincubated with LC were found in the ears but not in the lymph nodes upon i.v. injection. This finding shows that the migratory behavior can be reprogrammed by tissue-specific DC and may have input on strategies trying to use Treg not only for the prevention but also for the treatment of immune-mediated diseases.