Lessin S R, Vowels B R, Rook A H
Department of Dermatology, University of Pennsylvania, Philadelphia.
Dermatol Clin. 1994 Apr;12(2):243-53.
Since the discovery of the first human retrovirus, HTLV-I, and its etiologic role in ATL, the search for a retrovirus and its role in the development and progression of CTCL has been vigorously pursued and debated. Current studies in CTCL have evaluated serum antibodies to retroviral proteins, electron microscopy to identify viruslike particles, and Southern blot analysis and PCR amplification to detect proviral DNA sequences. There have been inconsistent findings within and between a variety of studies, emphasizing the need for critical evaluation of experimental methods and their potential shortcomings. Several interesting observations have included (1) serologic evidence of HTLV-I infection in a small subset of CTCL patients, (2) cloning of a deleted HTLV-I proviral genome from a B-cell line established from the peripheral blood of a CTCL patient, (3) detection of retrovirus in Langerhans cells and B cells, and (4) molecular evidence for the presence of an HTLV-I-like retrovirus. By viewing CTCL as a model of tumor progression, mechanisms by which retroviruses play a role in the development and progression of CTCL are facilitated. Future studies will need to correlate the detection of proviral sequences and the nature of a retroviral infection with specific cell types and stage of disease and determine if these findings demonstrate a causal role in CTCL or a secondary phenomenon due to CTCL-associated immunosuppression. It is likely that new data will be reported between the writing of this article and the time of publication; however, the currently available data reviewed in this article do not provide conclusive evidence that retroviruses play a primary etiologic role in CTCL.
自从发现首例人类逆转录病毒HTLV-I及其在成人T细胞白血病(ATL)中的病因学作用以来,人们一直在积极探索逆转录病毒及其在蕈样肉芽肿(CTCL)发生发展过程中的作用,并展开了激烈的争论。目前针对CTCL的研究评估了血清中针对逆转录病毒蛋白的抗体、用于识别病毒样颗粒的电子显微镜检查,以及用于检测前病毒DNA序列的Southern印迹分析和PCR扩增。各类研究内部及相互之间的结果并不一致,这凸显了对实验方法及其潜在缺陷进行严格评估的必要性。一些有趣的观察结果包括:(1)一小部分CTCL患者存在HTLV-I感染的血清学证据;(2)从一名CTCL患者外周血建立的B细胞系中克隆出缺失的HTLV-I前病毒基因组;(3)在朗格汉斯细胞和B细胞中检测到逆转录病毒;(4)存在HTLV-I样逆转录病毒的分子证据。将CTCL视为肿瘤进展模型,有助于理解逆转录病毒在CTCL发生发展过程中发挥作用的机制。未来的研究需要将前病毒序列的检测以及逆转录病毒感染的性质与特定细胞类型和疾病阶段相关联,并确定这些发现是否表明其在CTCL中具有因果作用,还是CTCL相关免疫抑制导致的继发现象。在本文撰写至发表期间可能会有新的数据报道;然而,本文所综述的现有数据并未提供确凿证据表明逆转录病毒在CTCL中起主要病因作用。