Identification and quantitation of interferon-γ producing T cells in psoriatic lesions:: Localization to both CD4+ and CD8+ subsets
Identification and quantitation of interferon-γ producing T cells in psoriatic lesions:: Localization to both CD4+ and CD8+ subsets
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DOI：
10.1046/j.1523-1747.1998.00419.x
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发表时间：
1998-12-01
影响因子：
6.5
通讯作者：
Cooper, KD
中科院分区：
文献类型：
--
作者：
Szabo, SK;Hammerberg, C;Cooper, KD
病变 T 细胞克隆产生的干扰素-γ (IFN-γ) 对于银屑病角质形成细胞干细胞诱导进入细胞周期 G1 至关重要；然而，缺乏证明银屑病病变 T 细胞亚群 IFN-γ 表达的直接数据，以及在单细胞水平上进行定量以计算体内比例的数据。在这项研究中，我们使用流式细胞术对角膜刀活检中新鲜分离的正常和银屑病病变 T 细胞进行分析，发现与正常人相比，银屑病皮肤的所有区室中 CD3(+)、CD4(+) 和 CD8(+) T 细胞均升高。使用 Brefeldin A 诱导能够产生 IFN-γ 的 T 细胞短期内积累 IFN-γ，我们发现 90% 的银屑病患者的 CD3(+) 细胞中产生 IFN-γ 的 T 细胞比例高于正常人，平均为 16% +/- 3%，而正常表皮中为 4% +/- 2% (p = 0.01)。组织中，银屑病表皮中的 IFN-gamma(+) CD3(+) 细胞数为每 mm(2) 表面积 97 +/- 22 个，而正常表皮为 4.4 +/- 1.8 个/mm(2) (p = 0.002)。因此，20% 受累患者皮肤中 IFN-gamma(+) CD3(+) T 细胞的总数估计为 3.9 X 10(8)。相对于正常皮肤，银屑病牛皮癣中 CD4(+) 和 CD8(+) IFN-gamma(+) T 细胞均升高（分别为 p = 0.04 和 p = 0.008）。在真皮中，只有 44% 的患者表现出比正常人更高比例的产生 IFN-γ 的 T 细胞 (p = 0.1)，这可能表明在某些患者中，被新鲜浸润的 T 细胞稀释。流式细胞术、逆转录酶-聚合酶链式反应、蛋白质印迹和免疫沉淀的组合未发现 Interleukin-4。总之，银屑病中很大一部分病变 T 细胞产生 IFN-γ，但不产生 IL-4。 IFN-γ(+) CD4(+) 和 IFN-γ(+) CD8(+) T 细胞数量增加表明 CD4(+) 和 CD8(+) IFN-γ(+) T 细胞存在于适当的解剖位置以维持病变病理。
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 mm(2) surface area, as compared with 4.4 +/- 1.8 per mm(2) 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 kepidermis (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.