Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege
Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege
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DOI：
10.1158/0008-5472.can-06-0261
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发表时间：
2006-06-01
期刊：
影响因子：
11.2
通讯作者：
Ueda, Ryuzo
中科院分区：
文献类型：
--
作者：
Ishida, Takashi;Ishii, Toshihiko;Ueda, Ryuzo
霍奇金淋巴瘤（HL）的特征是在丰富的炎性细胞背景中存在少量的肿瘤细胞，但大量的非肿瘤细胞对HL发病机制的贡献知之甚少。我们发现，HL细胞诱导的迁移性CD 4（+）细胞对T细胞受体刺激反应迟钝，并抑制了自体环境中效应CD 4（+）T细胞的活化/增殖。我们进一步表明，HL细胞在受影响的淋巴结被大量的淋巴细胞表达CC趋化因子受体4（CCR 4）和FOXP 3。这些结果表明，HL细胞诱导的迁移细胞具有调节性T（Treg）细胞的功能，从而为肿瘤细胞逃离宿主免疫系统创造了有利的环境。此外，我们发现嵌合抗CCR 4单克隆抗体（mAb）可以在体外清除CCR 4（+）T细胞，并抑制CD 4（+）CD 25（+）T细胞的迁移。认识到CCR 4（+）Treg细胞在HL发病机制中的重要性将允许合理设计更有效的治疗，例如使用抗CCR 4 mAb，以克服CCR 4（+）Treg细胞对宿主对肿瘤细胞的免疫应答的抑制作用。
Hodgkin lymphoma (HL) is characterized by the presence of a small number of tumor cells in a rich background of inflammatory cells, but the contribution of the abundant nontumor cells to HL pathogenesis is poorly understood. We showed that migratory CD4(+) cells induced by HL cells were hyporesponsive to T-cell receptor stimulation and suppressed the activation/proliferation of the effector CD4(+) T cells in an autologous setting. We further showed that HL cells in the affected lymph nodes were surrounded by a large number of lymphocytes expressing both CC chemokine receptor 4 (CCR4) and FOXP3. These findings indicate that the migratory cells induced by HL cells function as regulatory T (Treg) cells so that these cells create a favorable environment for the tumor cells to escape from host immune system. In addition, we showed that a chimeric anti-CCR4 monoclonal antibody (mAb) could deplete CCR4(+) T cells and inhibit the migration of CD4(+)CD25(+) T cells in vitro. Recognition of the importance of CCR4(+) Treg cells in the pathogenesis of HL will allow rational design of more effective treatments, such as use of an anti-CCR4 mAb, to overcome the suppressive effect of CCR4(+) Treg cells on the host immune response to tumor cells.