The majority of epidermal T cells in Psoriasis vulgaris lesions can produce type 1 cytokines, interferon-γ, interleukin-2, and tumor necrosis factor-α, defining TC1 (cytotoxic T lymphocyte) and TH1 effector populations:: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients
The majority of epidermal T cells in Psoriasis vulgaris lesions can produce type 1 cytokines, interferon-γ, interleukin-2, and tumor necrosis factor-α, defining TC1 (cytotoxic T lymphocyte) and TH1 effector populations:: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients
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DOI：
10.1046/j.1523-1747.1999.00749.x
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发表时间：
1999-11-01
影响因子：
6.5
通讯作者：
Krueger, JG
中科院分区：
文献类型：
--
作者：
Austin, LM;Ozawa, M;Krueger, JG
寻常型银屑病是一种可能由1型皮损T细胞产生的促炎细胞因子介导的皮肤病。皮损皮肤中单个T细胞产生这些细胞因子的能力尚不清楚。在这项研究中，我们用流式细胞仪检测了皮损和外周血T细胞产生细胞内干扰素-γ、肿瘤坏死因子-α、白介素2、白介素4和白介素10蛋白的能力。细胞因子的合成是在Brefeldin A的存在下，通过离子霉素/佛波酯的激活来诱导的，Brefeldin A可以抑制这些细胞因子的胞吐。刺激后，我们发现表皮CD8和CD4T细胞能够产生干扰素-γ、肿瘤坏死因子-α和白介素2的比例相对较高，而表达白介素4或白介素10的T细胞很少，仅占11%。因此，CD8(+)和CD4(+)T细胞都具有1型效应功能(分别为Tc1和TH1)，我们在银屑病患者和健康对照组的外周血T细胞上重复了这种激活方案，我们也发现了1型偏向。为了定量评估1型细胞因子的偏向，我们在我们的检测中比较了产生2型白介素4和1型干扰素-γ的T细胞的频率，发现产生1型细胞的转变，这种转变揭示了皮损区域和外周血中的1型分化倾向，这可能表明T细胞群体内的失衡，这是导致本病T细胞慢性或持续的免疫激活的原因之一。
Psoriasis vulgaris is a skin disease potentially mediated by pro-inflammatory cytokines produced by type 1 lesional T cells. The capability of individual T cells to produce these cytokines in lesional skin is not known. In this study we measured the ability of lesional and peripheral blood T cells to produce intracellular interferon-gamma, tumor necrosis factor-alpha, interleukin-2, interleukin-4, and interleukin-10 proteins as detected by flow cytometric analysis. Cytokine synthesis was induced by activation with ionomycin/phorbol myristate acetate tin the presence of Brefeldin A, which inhibits the exocytosis of these cytokines). After stimulation, we found relatively high percentages of epidermal CD8 and CD4 T cells capable of producing interferon-gamma, tumor necrosis factor-alpha, and interleukin-2, whereas few T cells, < 11%, expressed interleukin-4 or interleukin-10. Hence both CD8(+) and CD4(+) T cells are capable of type 1 effector functions (TC1 and TH1, respectively), This activation scheme was repeated on peripheral blood T cells from psoriatic patients versus healthy controls, where we also found a type 1 bias. In order to evaluate quantitatively the type 1 cytokine bias, we compared the frequency of type 2 interleukin-4 producing versus type 1 interferon-gamma producing T cells in our assay and found a shift towards type 1 producing cells, This shift reveals a type 1 differentiation bias in both lesional areas and in the peripheral blood, which may indicate an imbalance within the T cell population, which is contributing to the chronic or sustained immunologic activation of T cells found in this disease.