Asadullah K, Friedrich M, Döcke W D, Jahn S, Volk H D, Sterry W
Department of Dermatology, Medical School Charité, Humboldt UniversityBerlin, Germany.
J Invest Dermatol. 1997 May;108(5):743-7. doi: 10.1111/1523-1747.ep12292129.
Indolent, primary cutaneous T-cell lymphomas (CTCL) are characterized by hyper-proliferation of malignant T-helper cells in the skin with a favorable prognosis in the early stages. Cytotoxic T cells (CTLs) are believed to be of major importance for tumor surveillance, but there is not yet sufficient evidence for a systemic anti-tumor response in mycosis fungoides (MF). On the contrary, there are hints of systemic immunodepression. We wondered whether signs of a systemic anti-tumor response were demonstrable in peripheral blood of patients with MF and CD30+ pleomorphic T cell lymphoma. Using multiparameter flow cytometry, we investigated blood samples from 39 CTCL patients at different stages and compared them with those from patients with psoriasis, atopic dermatitis, and healthy volunteers. In CTCL patients, an elevated number of lymphocytes expressing natural killer cell markers were found, as well as considerable T-cell activation, indicated by increased percentages of T cells expressing HLA-DR, IL-2 receptor alpha-chain, and transferrin receptor. The CD8+ T cells, which were the most strongly activated T-cell subset, were of polyclonal origin, as shown by their usage of different T-cell receptor families. The enhanced expression of activation antigens was associated with an increased proportion of CD8+ T cells with high expression of the adhesion molecule LFA-1, demonstrating the capacity for migration of these cells. These CD8+ effector cells are suspected to be CTLs and may be responsible for the favorable prognosis of indolent, primary CTCL. Interestingly, a stage-dependent decrease in T-cell activation antigen expression was observed, suggesting the development of a lack in tumor surveillance in advanced MF stages. Further investigations are necessary to verify whether any of the parameters determined are of predictive value for prognosis and response to therapy in CTCL.
惰性原发性皮肤T细胞淋巴瘤（CTCL）的特征是皮肤中恶性辅助性T细胞过度增殖，早期预后良好。细胞毒性T细胞（CTL）被认为对肿瘤监测至关重要，但蕈样肉芽肿（MF）中尚无足够证据表明存在全身性抗肿瘤反应。相反，有全身性免疫抑制的迹象。我们想知道MF和CD30 +多形性T细胞淋巴瘤患者的外周血中是否可显示出全身性抗肿瘤反应的迹象。我们使用多参数流式细胞术研究了39例不同阶段CTCL患者的血样，并将其与银屑病、特应性皮炎患者及健康志愿者的血样进行比较。在CTCL患者中，发现表达自然杀伤细胞标志物的淋巴细胞数量增加以及T细胞显著激活，这表现为表达HLA-DR、IL-2受体α链和转铁蛋白受体的T细胞百分比增加。最强烈激活的T细胞亚群CD8 + T细胞起源多克隆，这可通过其对不同T细胞受体家族的使用情况来表明。激活抗原的表达增强与高表达黏附分子LFA-1的CD8 + T细胞比例增加有关，表明这些细胞具有迁移能力。这些CD8 +效应细胞被怀疑是CTL，并可能是惰性原发性CTCL预后良好的原因。有趣的是，观察到T细胞激活抗原表达呈阶段依赖性下降，这表明晚期MF阶段肿瘤监测功能缺失。有必要进一步研究以验证所测定参数中是否有任何参数对CTCL的预后和治疗反应具有预测价值。
