Ballieux B E, van der Burg S H, Hagen E C, van der Woude F J, Melief C J, Daha M R
Department of Nephrology, University Hospital, Leiden, The Netherlands.
Clin Exp Immunol. 1995 May;100(2):186-93. doi: 10.1111/j.1365-2249.1995.tb03651.x.
Despite the well described infiltration of cells of the cellular immune system in vasculitic lesions and the granuloma formation in patients with WG, the role of T cell-mediated autoimmunity in WG is not clear. Reports of T cell proliferation in response to neutrophil azurophilic granule proteins are contradictory. In this study we have assessed the proliferation of T cells of WG patients to purified proteinase 3 (PR3) and to total azurophilic granule proteins in two different assays. In addition to the classical proliferation assay with isolated peripheral blood mononuclear cells, we have used a whole blood proliferation assay. In both assays we found proliferative responses to PR3 in patients with WG. The number of patients reacting to the azurophilic granule extract was higher than the patients reacting to the purified PR3, suggesting that other autoantigens may also be involved. We have identified epitopes of PR3 that may be potential targets of class I-restricted T cell responses in the context of HLA-A0201, the most common MHC class I molecule. These epitopes were determined by the binding of synthetic PR3 peptides to HLA-A0201 on the antigen-processing defective cell line, T2. In addition, T cell lines were established from tissue biopsies, obtained from WG patients, and assessed for cytolytic reactivity against T2 cells, preloaded with synthetic PR3 peptides. We conclude that T lymphocytes of WG patients have increased proliferative responses to purified PR3 and to a larger extent to non-fractionated proteins of azurophilic granules of polymorphonuclear neutrophilic leucocytes (PMN).
尽管在血管炎病变中细胞免疫系统细胞的浸润以及韦格纳肉芽肿病（WG）患者中肉芽肿形成已有详尽描述，但T细胞介导的自身免疫在WG中的作用尚不清楚。关于T细胞对中性粒细胞嗜天青颗粒蛋白反应性增殖的报道相互矛盾。在本研究中，我们通过两种不同检测方法评估了WG患者T细胞对纯化蛋白酶3（PR3）和总嗜天青颗粒蛋白的增殖情况。除了使用分离的外周血单个核细胞进行经典增殖检测外，我们还采用了全血增殖检测。在两种检测中，我们均发现WG患者对PR3有增殖反应。对嗜天青颗粒提取物产生反应的患者数量高于对纯化PR3产生反应的患者，这表明可能还涉及其他自身抗原。我们已鉴定出PR3的表位，在最常见的MHC I类分子HLA - A0201背景下，这些表位可能是I类限制性T细胞反应的潜在靶点。这些表位是通过合成PR3肽与抗原加工缺陷细胞系T2上的HLA - A0201结合来确定的。此外，从WG患者的组织活检中建立T细胞系，并评估其对预负载合成PR3肽的T2细胞的细胞溶解反应性。我们得出结论，WG患者的T淋巴细胞对纯化PR3的增殖反应增强，并且在更大程度上对多形核嗜中性白细胞（PMN）嗜天青颗粒的未分级蛋白有增殖反应。
