Thumann P, Lüftl M, Moc I, Bagot M, Bensussan A, Schuler G, Jenne L
Department of Dermatology, University Hospital Erlangen, Hartmannstrasse 14, 91052 Erlangen, Germany.
Br J Dermatol. 2003 Dec;149(6):1128-42. doi: 10.1111/j.1365-2133.2003.05674.x.
Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of skin neoplasms that originate from T lymphocytes. An anti-CTCL T-cell immunity has been described but seems to be inefficient to clear CTCL cells. It is not known whether cutaneous dendritic cells (DCs) perpetuate the proliferation of the malignant CTCL cell clone or play a role in the control of this usually slowly progressing disease.
To characterize CTCL cell properties in the control of anti-CTCL T cells and to pave the way for a DC-based immunotherapy for CTCL.
We studied the interaction of a CTCL cell line with DCs and with allogeneic T cells.
We found an antigen non-specific capacity of viable but not apoptotic CTCL cells to hamper CD4+ and CD8+ T-cell proliferation in a dose-dependent manner, indicating a suppressive potential of CTCL cells. Both viable and apoptotic CTCL cells were phagocytosed by immature DCs but only apoptotic CTCL cells induced an upregulation of DC maturation markers to a degree which enabled classification of these DCs as semimature. CTCL cells did not respond with proliferation when encountering allogeneic, mature DCs either loaded with CTCL cell material or unloaded, indicating a role for DCs in the induction of anti-CTCL T-cell immunity rather than in perturbation of clonal proliferation. For the loading of DCs with CTCL material lysate seems to be optimal as apoptotic cells were not phagocytosed extensively and necrotic CTCL material induced a partial cellular toxicity in DCs. DCs loaded with CTCL material were cryopreservable without significant loss of DC viability, surface marker expression or allostimulatory activity.
Together, these data argue in favour for a DC-based immunotherapy for CTCL patients and provide an experimental protocol for preparing CTCL cell-loaded DCs.
皮肤T细胞淋巴瘤（CTCL）是一组起源于T淋巴细胞的异质性皮肤肿瘤。已有抗CTCL T细胞免疫的相关描述，但似乎在清除CTCL细胞方面效率不高。目前尚不清楚皮肤树突状细胞（DC）是促进恶性CTCL细胞克隆的增殖，还是在控制这种通常进展缓慢的疾病中发挥作用。
明确CTCL细胞在抗CTCL T细胞控制中的特性，为基于DC的CTCL免疫治疗铺平道路。
我们研究了一种CTCL细胞系与DC以及同种异体T细胞之间的相互作用。
我们发现活的而非凋亡的CTCL细胞具有抗原非特异性能力，可剂量依赖性地抑制CD4 +和CD8 + T细胞增殖，表明CTCL细胞具有抑制潜能。活的和凋亡的CTCL细胞均可被未成熟DC吞噬，但只有凋亡的CTCL细胞能诱导DC成熟标志物上调至一定程度，使这些DC可被归类为半成熟DC。当遇到负载或未负载CTCL细胞材料的同种异体成熟DC时，CTCL细胞不会发生增殖反应，这表明DC在诱导抗CTCL T细胞免疫中起作用，而非干扰克隆增殖。对于用CTCL材料负载DC，裂解物似乎是最佳选择，因为凋亡细胞不会被大量吞噬，而坏死的CTCL材料会在DC中诱导部分细胞毒性。负载CTCL材料的DC可冷冻保存，而不会显著丧失DC活力、表面标志物表达或同种异体刺激活性。
总之，这些数据支持对CTCL患者进行基于DC的免疫治疗，并提供了制备负载CTCL细胞的DC的实验方案。
