Schlaak J F, Buslau M, Jochum W, Hermann E, Girndt M, Gallati H, Meyer zum Büschenfelde K H, Fleischer B
First Department of Medicine, University of Mainz, Germany.
J Invest Dermatol. 1994 Feb;102(2):145-9. doi: 10.1111/1523-1747.ep12371752.
Although the pathogenesis of psoriasis vulgaris is still unknown, several characteristics point to an immunologically mediated process. Epidermal psoriatic lesions are characterized by a hyperproliferation of keratinocytes and an infiltration of T lymphocytes and granulocytes. Because the former may be mediated in part by lymphokines secreted by T cells, we have focused our interest on the in vivo and in vitro cytokine secretion patterns of T lymphocytes from psoriatic lesions. In five patients T lymphocytes were obtained from epidermal specimens. The cells were propagated with lectin and irradiated feeder cells and subsequently cloned by limiting dilution. The resulting T-cell clones were phenotypically and functionally characterized. Our data show that the majority of T-cell clones were CD4+ (74%), whereas only 25% were CD8+ and 1% were CD4-/CD8-. Also, we have further investigated the cytokine secretion pattern of T-cell lines or CD4+ T-cell clones, respectively. All cells tested produced interferon-gamma whereas only a minority secreted interleukin (IL)-4. Moreover, these cells produced high amounts of IL-2 but only little or no IL-10 or tumor necrosis factor-alpha. To correlate these data with the in vivo situation, biopsies from psoriatic lesions of five patients were investigated for the presence of the mRNA of IL-4, IL-10, and interferon-gamma using the polymerase chain reaction. In these biopsies only the mRNA for the Th1 cytokine interferon-gamma but not for the Th2 cytokines IL-4 and IL-10 could be detected. Identical experiments were performed to test the in vivo cytokine production of synovial fluid mononuclear cells of two patients with arthropathia psoriatica. Again, only the mRNA for interferon-gamma but not IL-4 could be detected. This indicates that T cells involved in psoriasis exhibit a Th1-like cytokine secretion profile.
虽然寻常型银屑病的发病机制尚不清楚,但一些特征表明这是一个免疫介导的过程。银屑病的表皮病变特征为角质形成细胞过度增殖以及T淋巴细胞和粒细胞浸润。由于前者可能部分由T细胞分泌的淋巴因子介导,我们将兴趣集中在银屑病皮损中T淋巴细胞的体内和体外细胞因子分泌模式上。从5名患者的表皮标本中获取T淋巴细胞。这些细胞用凝集素和经辐照的饲养细胞进行增殖,随后通过有限稀释法进行克隆。对所得的T细胞克隆进行表型和功能鉴定。我们的数据显示,大多数T细胞克隆为CD4+(74%),而只有25%为CD8+,1%为CD4-/CD8-。此外,我们分别进一步研究了T细胞系或CD4+ T细胞克隆的细胞因子分泌模式。所有测试细胞均产生γ干扰素,而只有少数细胞分泌白细胞介素(IL)-4。而且,这些细胞产生大量IL-2,但仅产生少量或不产生IL-10或肿瘤坏死因子-α。为了将这些数据与体内情况相关联,使用聚合酶链反应对5名患者银屑病皮损的活检标本进行研究,以检测IL-4、IL-10和γ干扰素的mRNA。在这些活检标本中,仅可检测到Th1细胞因子γ干扰素的mRNA,而未检测到Th2细胞因子IL-4和IL-10的mRNA。对两名银屑病关节炎患者的滑液单核细胞进行体内细胞因子产生检测,进行了相同的实验。同样,仅可检测到γ干扰素的mRNA,而未检测到IL-4的mRNA。这表明参与银屑病的T细胞表现出类似Th1的细胞因子分泌谱。