Sezary syndrome T-cell clones display T-helper 2 cytokines and express the accessory factor-1 (Interferon-gamma receptor beta-chain)
Sezary syndrome T-cell clones display T-helper 2 cytokines and express the accessory factor-1 (Interferon-gamma receptor beta-chain)
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DOI：
10.1182/blood.v88.4.1383.bloodjournal8841383
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发表时间：
1996-08-15
期刊：
影响因子：
20.3
通讯作者：
Burg, G
中科院分区：
文献类型：
--
作者：
Dummer, R;Heald, PW;Burg, G
Sezary综合征（SS）是一种低级别皮肤t细胞淋巴瘤（CTCLs）的白血病变体。这种淋巴增生性疾病的克隆T细胞特征不明显。利用针对t细胞受体可变区（TCR V α / β）的抗体，我们在SS患者外周血单核细胞（PBMC）中鉴定出4个主要的t细胞克隆(2个V β 8（+）克隆，1个V β 5.1（+）克隆和1个V α 2（a)（+）克隆）。其表型为CD3（+）、CD4（+）、CD5（+）、CD45RO（+）。纯化克隆T细胞，用逆转录聚合酶链反应（RT-PCR）分析细胞因子的转录和分泌，然后用生物素化探针和酶联免疫吸附法（elisa）杂交。对IL-10 (interleukin-10, IL-10) PCR产物进行克隆和测序，发现与已发表的cDNA序列相同。用重组人AF-1蛋白胞外结构域免疫兔的血清，通过RT-PCR和免疫染色，评估辅助因子-1 （AF-1，或干扰素- γ [ifn - γ]受体β链）编码mRNA的存在，然后进行APAAP染色。克隆T细胞主要转录和分泌辅助性T细胞因子（IL-10、-5和-13）。纯化SS克隆的mRNA在琼脂糖凝胶和/或杂交后呈AF-1阳性，但SS总PBMC的mRNA未呈阳性。在SS克隆中，AF-1的转录与AF-1的膜结合免疫反应性相关。ss衍生的t细胞克隆显示辅助t - 2细胞因子。这削弱了细胞介导的免疫监视，并解释了SS患者的临床和免疫异常。所有克隆的辅助t - 2细胞因子谱都与AF-1的过表达有关。这表明AF-1是这些克隆（最终是其他t -辅助性2淋巴细胞）的潜在标记物，可能代表治疗该疾病的靶标。(C) 1996年由美国血液病学会出版。
Sezary syndrome (SS) is a leukemic variant of low-grade cutaneous T-cell lymphomas (CTCLs). The clonal T cells in this lymphoproliferative disorder are poorly characterized. Using antibodies against the variable region of the T-cell receptor (TCR V alpha/beta), we identified four predominant T-cell clones (two V beta 8(+) clones, one V beta 5.1(+), and one V alpha 2(a)(+)) in peripheral blood mononuclear cells (PBMC) of SS patients. Their phenotype was CD3(+), CD4(+), CD5(+) CD45RO(+). Clonal T cells were purified, and cytokine transcription and secretion was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) followed by hybridization with biotinylated probes and enzyme-linked immunosorbent assays (ELISAs). The interleukin-10 (IL-10) PCR product was cloned and sequenced and found to be identical to the published cDNA sequence. The presence of accessory factor-1 (AF-1, or interferon-gamma [IFN-gamma] receptor beta-chain) encoding mRNA was assessed by RT-PCR and immunostaining using serum of rabbits immunized with the extracellular domain of a recombinant human AF-1 protein followed by APAAP staining. Clonal T cells transcribe and secrete mainly T-helper 2 cytokines (IL-10, -5, and -13). mRNA from purified SS clones but not mRNA from SS total PBMC was positive for AF-1 in an agarose gel and/or after hybridization. AF-1 transcription was associated with membrane-bound immunoreactivity for AF-1 in SS clones. SS-derived T-cell clones display T-helper 2 cytokines. This weakens cell-mediated immunosurveillance, and explains the clinical and immunologic abnormalities in SS patients. The T-helper 2 cytokine spectrum of all clones investigated is associated with overexpression of AF-1. This suggests that AF-1 is a potential marker for these clones (and eventually other T-helper 2 lymphocytes) and might represent a target for treatment of the disease. (C) 1996 by The American Society of Hematology.