TH2 CYTOKINE MESSENGER-RNA EXPRESSION IN SKIN IN CUTANEOUS T-CELL LYMPHOMA

TH2 CYTOKINE MESSENGER-RNA EXPRESSION IN SKIN IN CUTANEOUS T-CELL LYMPHOMA
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DOI:
10.1111/1523-1747.ep12398454
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发表时间:
1994-11-01
影响因子:
6.5
通讯作者:
ROOK, AH
ROOK, AH
中科院分区:
医学1区
文献类型:
--
作者:
VOWELS, BR;LESSIN, SR;ROOK, AH

文献摘要

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我们先前已经证明,Sezary综合征患者的外周血单个核细胞具有Th2细胞细胞因子[IL-4和IL-5]的产生模式。Sezary综合征是一种皮肤T细胞淋巴瘤的白血病形式,伴有红皮病和淋巴结病。在这项研究中,我们扩展了这些观察,以证明在皮肤T细胞淋巴瘤(CTCL)患者皮肤受累的不同阶段,Th2细胞因子模式的存在与恶性T细胞克隆的相关性。其中CTCL患者12例(斑块3例,斑块3例,肿瘤6例),副银屑病3例,炎症性皮肤病4例,其中银屑病2例,扁平苔藓2例,正常对照12例。提取总RNA,逆转录,用IL-2、IL-4、IL-5、干扰素-γ和β-肌动蛋白寡核苷酸引物进行聚合酶链式反应。虽然所有被检测的皮肤标本都检测到IL-2和干扰素-γ的mRNA,但只有CTCL或副银屑病患者的皮肤标本才有IL-4和/或IL-5mRNA的表达。在6例肿瘤期CTCL中5例、3例斑块期CTCL中2例、3例斑块期CTCL中1例、3例副银屑病患者中1例皮肤活检组织中检测到IL-5mRNA,而在5例肿瘤期CTCL、1例斑块期CTCL、3例斑块期CTCL和3例副银屑病患者中均未检测到IL-4mRNA。结果表明,在CTCL皮肤受累的各个阶段,从斑块期到肿瘤期,IL-4和IL-5mRNA均有不同程度的表达。在肿瘤阶段的皮肤病变中,通常以致密的真皮恶性T细胞浸润为特征,Th2细胞因子mRNA几乎总是可以检测到。在CTCL患者皮肤中检测Th2细胞因子mRNA的能力支持了我们先前的发现,即CTCL中的恶性T细胞具有Th2辅助细胞表型。
We have previously demonstrated that peripheral blood mononuclear cells from patients with Sezary syndrome, the leukemic form of cutaneous T-cell lymphoma which is accompanied by erythroderma and lymphadenopathy, have a Th2 cell cytokine [interleukin 4 (IL-4) and interleukin 5] production pattern. In this study, we extend these observations to demonstrate a correlation of the presence of a Th2 cytokine pattern with a malignant T-cell clone in different stages of cutaneous involvement among patients with cutaneous T-cell lymphoma (CTCL). Skin biopsies were obtained from 12 CTCL patients with various disease stages (three patch, three plaque, six tumor), three patients with parapsoriasis, four patients with inflammatory dermatoses, including two psoriasis and two lichen planus, and 12 normal controls. Total RNA was extracted, reverse transcribed, and PCR amplified with IL-2, IL-4, IL-5, interferon gamma (IFN-gamma), and beta-actin oligonucleotide primers. Although all skin specimens tested had detectable IL-2 and IFN-gamma mRNA, only specimens from patients with CTCL or parapsoriasis had demonstrable IL-4 and/or IL-5 mRNA. Specifically, IL-5 mRNA was detected in skin biopsies from five of six tumor-stage CTCL, two of three plaque-stage CTCL, one of three patch-stage CTCL, and 1 of 3 parapsoriasis patients, whereas IL-4 mRNA was demonstrated to be present in five of six tumor-stage, one of three plaque stage, none of three patch-stage CTCL, and none of three parapsoriasis patients. These results indicate that in all stages of cutaneous involvement of CTCL, encompassing patch stage through tumor stage, IL-4 and IL-5 mRNA is variably detectable. In tumor-stage skin lesions, typically characterized by a dense dermal infiltrate of malignant T cells, Th2 cytokine mRNA is virtually always detectable. The ability to detect Th2 cytokine mRNA in the skin of patients with CTCL supports our previous findings that the malignant T cells in CTCL possess a Th2-helper cell phenotype.