Bagot M
Service de Dermatologie et INSERM U448, Hôpital Henri Mondor, Créteil.
Bull Acad Natl Med. 1998;182(5):927-37; discussion 937-8.
In 1938, Sézary and Bouvrain reported a new form of disseminated cutaneous lymphomas, characterized by an erythrodermia, and by the presence in the blood of cells with a cerebriform nucleus. It was shown later that this disease was related to the proliferation of a subpopulation of CD4+ T lymphocytes. With the aim to develop new therapeutic strategies for these lymphomas, we tried to evidence and to characterize the tumor-specific immune responses in these cutaneous T-cell lymphomas. We have isolated several T cell clones from lymphocytes infiltrating a human MHC class II negative cutaneous T cell lymphoma. We describe here two of these clones, TC5 and TC7, with respectively a CD4+CD8+ and CD4+CD8- phenotype. Both clones mediated a specific MHC class I-restricted cytotoxic activity toward the fresh autologous tumor cells, and autologous tumor cell lines previously established with IL-2 and IL-7 from the skin and from the blood. Analysis of the T-cell receptor V beta gene expression revealed that the tumor cells, that were shown to have a trisomy 7 by fluorescent in situ hybridization, expressed V beta 7/J beta 2.3, V beta 13/J beta 2.5 and V beta 22/J beta 2.5 rearrangements. Phenotypic analysis using specific anti-V beta monoclonal antibodies indicated that only V beta 13 could be detected on the cell membrane of the tumor cells. Analysis of the TCR V beta gene expression of the clones showed that TC5 and TC7 expressed a unique TCR-V beta transcript, corresponding respectively to V beta 5/J beta 2.3 and V beta 17/J beta 2.7 gene segments. To determine whether these reactive T lymphocytes were present in vivo, we used specific primers corresponding to TC5 and TC7-V beta TCR transcripts. The results demonstrated that both cytotoxic T cell clones were present at the lesional skin site and amplified in vitro. TC7 was found in the patient peripheral blood invaded by tumoral cells, whereas TC5 was not, indicating that the repertoire of the reactional lymphocytes differs in the blood and at the tumor site. These results demonstrate for the first time the presence of reactive T lymphocytes with CD4 or double positive phenotype infiltrating a CTCL. These findings raise new perspectives for the treatment of cutaneous T-cell lymphomas.
1938年，塞扎里（Sézary）和布弗兰（Bouvrain）报道了一种新的播散性皮肤淋巴瘤，其特征为红皮病，且血液中存在脑回状核细胞。后来发现这种疾病与CD4 + T淋巴细胞亚群的增殖有关。为了开发针对这些淋巴瘤的新治疗策略，我们试图证明并表征这些皮肤T细胞淋巴瘤中的肿瘤特异性免疫反应。我们从浸润人类MHC II类阴性皮肤T细胞淋巴瘤的淋巴细胞中分离出了几个T细胞克隆。我们在此描述其中两个克隆，TC5和TC7，其表型分别为CD4 + CD8 +和CD4 + CD8 -。这两个克隆均介导了针对新鲜自体肿瘤细胞以及先前用来自皮肤和血液的IL - 2和IL - 7建立的自体肿瘤细胞系的特异性MHC I类限制性细胞毒性活性。对T细胞受体Vβ基因表达的分析表明，通过荧光原位杂交显示具有7号染色体三体性的肿瘤细胞表达Vβ7 / Jβ2.3、Vβ13 / Jβ2.5和Vβ22 / Jβ2.5重排。使用特异性抗Vβ单克隆抗体的表型分析表明，仅Vβ13可在肿瘤细胞膜上检测到。对克隆的TCR Vβ基因表达的分析表明，TC5和TC7表达独特的TCR - Vβ转录本，分别对应于Vβ5 / Jβ2.3和Vβ17 / Jβ2.7基因片段。为了确定这些反应性T淋巴细胞在体内是否存在，我们使用了与TC5和TC7 - VβTCR转录本相对应的特异性引物。结果表明，这两个细胞毒性T细胞克隆均存在于病变皮肤部位并在体外扩增。在肿瘤细胞侵袭的患者外周血中发现了TC7，而未发现TC5，这表明反应性淋巴细胞的库在血液和肿瘤部位有所不同。这些结果首次证明了具有CD4或双阳性表型的反应性T淋巴细胞浸润蕈样肉芽肿。这些发现为皮肤T细胞淋巴瘤的治疗提出了新的前景。
