[Cutaneous lymphoma of the Sézary and Bouvrain type. Progress in physiopathologic and therapeutic outlook].
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.
Bagot
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Service de Dermatologie et INSERM U448, Hôpital Henri Mondor, Créteil.
D005544:Forecasting; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000145:classification / Q000503:physiopathology / Q000628:therapy*; D012751:Sezary Syndrome / Q000503:physiopathology / Q000628:therapy*; D012878:Skin Neoplasms / Q000145:classification / Q000503:physiopathology / Q000628:therapy*