银屑病皮损中产生γ干扰素的T细胞的鉴定与定量：定位于CD4+和CD8+亚群。
Identification and quantitation of interferon-gamma producing T cells in psoriatic lesions: localization to both CD4+ and CD8+ subsets.
作者信息
Szabo S K, Hammerberg C, Yoshida Y, Bata-Csorgo Z, Cooper K D
机构信息
Department of Dermatology, Case Western Reserve University, University Hospitals of Cleveland, Ohio 44106, USA.
出版信息
J Invest Dermatol. 1998 Dec;111(6):1072-8. doi: 10.1046/j.1523-1747.1998.00419.x.
Interferon-gamma (IFN-gamma) produced by lesional T cell clones is critical for the induction into G1 of the cell cycle by psoriatic keratinocyte stem cells; however, direct data demonstrating psoriatic lesional T cell subset IFN-gamma expression, and quantitation at a single cell level to calculate in vivo proportions, are lacking. In this study, using flow cytometry of freshly isolated normal and psoriatic lesional T cells from keratome biopsies, we found elevated CD3+, CD4+, and CD8+ T cells in all compartments of psoriatic skin, compared with normals. Using Brefeldin A to induce short-term intracellular accumulation of IFN-gamma in T cells capable of IFN-gamma production, we found that 90% of psoriatic patients have IFN-gamma-producing T cells at a greater proportion of their CD3+ cells than normals, with a mean of 16%+/-3%, as compared with 4%+/-2% in normal epidermis (p = 0.01). Expressed as density in the tissue, the IFN-gamma+ CD3+ cell number in psoriatic epidermis was 97+/-22 per mm2 surface area, as compared with 4.4+/-1.8 per mm2 of normal epidermis (p = 0.002). Thus, the total number of IFN-gamma+CD3+ T cells in the skin of a patient with 20% involvement is estimated to be 3.9 x 10(8). CD4+ and CD8+ IFN-gamma+ T cells were both elevated in psoriatic epidermis (p = 0.04 and p = 0.008, respectively) relative to normal skin. In the dermis, only 44% of patients demonstrated a higher percentage of IFN-gamma-producing T cells than did normals (p = 0.1), possibly indicating dilution, in some patients, by fresh infiltrating T cells. Interleukin-4 was not found by a combination of flow cytometry, reverse transcriptase-polymerase chain reaction, western blot, and immunoprecipitation. In conclusion, a significant portion of lesional T cells in psoriasis are IFN-gamma producing, without interleukin-4. The increased numbers of both IFN-gamma+CD4+ and IFN-gamma+CD8+ T cells indicate that both CD4+ and CD8+ IFN-gamma+ T cells are present in appropriate anatomic locations to sustain the lesional pathology.
由皮损处T细胞克隆产生的干扰素-γ（IFN-γ）对于银屑病角质形成干细胞诱导进入细胞周期的G1期至关重要；然而，缺乏直接数据来证明银屑病皮损处T细胞亚群的IFN-γ表达情况以及在单细胞水平进行定量以计算体内比例。在本研究中，我们通过对角膜活检新鲜分离的正常和银屑病皮损处T细胞进行流式细胞术检测，发现与正常人相比，银屑病皮肤各区域的CD3⁺、CD4⁺和CD8⁺T细胞均增多。使用布雷菲德菌素A诱导能够产生IFN-γ的T细胞短期内胞内IFN-γ蓄积，我们发现90%的银屑病患者产生IFN-γ的T细胞在其CD3⁺细胞中所占比例高于正常人，平均为16%±3%，而正常表皮中为4%±2%（p = 0.01）。以组织密度表示，银屑病表皮中IFN-γ⁺CD3⁺细胞数量为每平方毫米表面积97±22个，而正常表皮为每平方毫米4.4±1.8个（p = 0.002）。因此，皮损面积为20%的患者皮肤中IFN-γ⁺CD3⁺T细胞总数估计为3.9×10⁸个。相对于正常皮肤，银屑病表皮中CD4⁺和CD8⁺IFN-γ⁺T细胞均增多（分别为p = 0.04和p = 0.008）。在真皮中，只有44%的患者产生IFN-γ的T细胞百分比高于正常人（p = 0.1），这可能表明在一些患者中，被新鲜浸润的T细胞稀释。通过流式细胞术、逆转录聚合酶链反应、蛋白质免疫印迹和免疫沉淀相结合的方法未检测到白细胞介素-4。总之，银屑病皮损处很大一部分T细胞能够产生IFN-γ，而不产生白细胞介素-4。IFN-γ⁺CD4⁺和IFN-γ⁺CD8⁺T细胞数量的增加表明CD4⁺和CD8⁺IFN-γ⁺T细胞均存在于适当的解剖位置以维持皮损病理状态。
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