Peripheral blood and granuloma CD4+CD28- T cells are a major source of interferon-γ and tumor necrosis factor-α in Wegener's granulomatosis
Peripheral blood and granuloma CD4+CD28- T cells are a major source of interferon-γ and tumor necrosis factor-α in Wegener's granulomatosis
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DOI：
10.1016/s0002-9440(10)61118-2
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发表时间：
2002-05-01
影响因子：
6
通讯作者：
Gross, WL
中科院分区：
文献类型：
--
作者：
Komocsi, A;Lamprecht, P;Gross, WL
为了阐明CD 4（+）T细胞群中CD 28（-）T细胞的比例是否是驱动韦格纳肉芽肿（WG）肉芽肿形成的Th 1样和促炎细胞因子产生的主要来源，我们分析了12例活动性WG患者外周血CD 4（+）CD 28（-）T细胞和肉芽肿病变中T细胞的表型和功能特征。通过流式细胞术评估表面标志物和胞浆内细胞因子和穿孔素表达。酶联免疫吸附试验测定细胞因子分泌。免疫组织学研究表明，干扰素-γ和肿瘤坏死因子-α细胞因子阳性归因于肉芽肿病变中的CD 4（+）CD 28（-）T细胞。外周血CD 4（+）CD 28（-）T细胞表达CD 57，也发现在自然杀伤细胞，和胞浆内穿孔素。他们通常是CD 25（白细胞介素-2受体）阴性。CD 18（粘附分子β（2）-整联蛋白）在CD 4（+）CD 28（-）T细胞上强烈上调，而只有少数CD 4（+）CD 28（+）T细胞表达CD 18。CD 4（+）CD 28（-）T细胞是IFN-γ和TNF-α的主要来源。相比之下，CD 4（+）CD 28（+）T细胞能够产生和分泌多种细胞因子，包括白细胞介素-2。四分之一的CD 4（+）CD 28（+）T细胞表达活化标记物CD 25，但它们缺乏穿孔素。因此，CD 4（+）CD 28（-）T细胞似乎比CD 4（+）CD 28（+）T细胞更分化。它们显示Th 1样细胞因子的产生和提示CD 4（+）T细胞介导的细胞毒性的能力的特征。CD 4（+）CD 28（-）T细胞可通过CD 18相互作用从血液中募集到肉芽肿性病变中，随后可通过其在WG中的细胞因子分泌促进单核细胞积聚和肉芽肿形成。
To elucidate whether the fraction of CD28(-) T cells within the CD4(+) T-cell population is a major source of Th1-like and proinflammatory cytokine production driving Wegener's granulomatosis (WG) granuloma formation, we analyzed the phenotype and functional characteristics of peripheral blood CD4(+)CD28(-) T cells and of T cells in granulomatous lesions of 12 patients with active WG. Surface markers and intracytoplasmic cytokine and perforin expression were assessed by flow cytometry. Cytokine secretion was measured by enzyme-linked immunosorbent assay. Immunohistological studies demonstrated interferon-gamma and tumor necrosis factor-alpha cytokine positivity attributable to CD4(+)CD28(-) T cells in granulomatous lesions. Peripheral blood CD4(+)CD28(-) T cells expressed CD57, also found on natural killer cells, and intracytoplasmic perforin. They were generally CD25 (interleukin-2 receptor)-negative. CD18 (adhesion molecule beta(2)-integrin) was strongly up-regulated on CD4(+)CD28(-) T cells, whereas only a minority of CD4(+)CD28(+) T cells expressed CD18. CD4(+)CD28(-) T cells appeared as a major source of interferon-gamma and tumor necrosis factor-a. In contrast, CD4(+)CD28(+) T cells were able to produce and secrete a wider variety of cytokines including interleukin-2. One-quarter of CD4(+)CD28(+) T cells expressed the activation marker CD25, but they lacked perforin. Thus, CD4(+)CD28(-) T cells appeared more differentiated than CD4(+)CD28(+) T cells. They displayed Th1-like cytokine production and features suggestive of the capability of CD4(+) T-cell-mediated cytotoxicity. CD4(+)CD28(-) T cells may be recruited into granulomatous lesions from the blood via CD18 interaction, and may subsequently promote monocyte accumulation and granuloma formation through their cytokine secretion in WG.