Development and characterization of desmoglein-3 specific T cells from patients with pemphigus vulgaris
Development and characterization of desmoglein-3 specific T cells from patients with pemphigus vulgaris
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DOI：
10.1172/jci119130
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发表时间：
1997-01-01
影响因子：
15.9
通讯作者：
Diaz, LA
中科院分区：
文献类型：
--
作者：
Lin, MS;Swartz, SJ;Diaz, LA
寻常天疱疮（PV）是一种皮肤自身免疫性疾病，其特征在于皮肤和粘膜的基底层上形成水疱，并且抗桥粒芯糖蛋白-3（Dsg 3）自身抗体结合至病变角质形成细胞表面并在患者血清中循环。通过被动转移患者IgG可使新生小鼠复制PV，提示体液免疫在PV的发病中起重要作用。目前，T淋巴细胞在PV发生发展中的作用尚不清楚。在这里，我们报告说，三个免疫反应性片段的胞外域的Dsg 3特异性诱导增殖的T细胞从PV患者。我们发现14名患者中有13名的T淋巴细胞对三种Dsg 3肽中的至少一种有反应。来自对照组和其他患者组的T细胞对这些Dsg 3肽没有应答。由这些Dsg 3肽刺激的主要T细胞群是CD 4阳性的。开发了Dsg 3特异性T细胞系和克隆，并显示其表达CD 4阳性记忆T细胞表型。在刺激后，这些细胞系和克隆分泌Th 2样细胞因子谱。这些T细胞的Dsg 3反应仅限于HLA-DR，而不是主要组织相容性复合体的-DQ和-DP。这些信息将有助于阐明导致PV患者产生致病性IgG自身抗体的细胞免疫异常。
Pemphigus vulgaris (PV) is a cutaneous autoimmune disease characterized by blister formation in the suprabasilar layers of skin and mucosae and anti-desmoglein-3 (Dsg3) autoantibodies bound to the surface of lesional keratinocytes and circulating in the serum of patients. This disease can be reproduced in neonatal mice by passive transfer of patients' IgG, indicating that humoral immunity plays an important role in the pathogenesis of PV. Currently, the role of T lymphocytes in the development of PV is not clear. Here, we report that three immunoreactive segments of the ectodomain of Dsg3 specifically induced proliferation of T cells from PV patients. We found that T lymphocytes from 13 out of 14 patients responded to at least one of three Dsg3 peptides. T cells from controls and other patient groups did not respond to these Dsg3 peptides. The major T cell population stimulated by these Dsg3 peptides was CD4 positive. Dsg3-specific T cell lines and clones were developed and were shown to express a CD4 positive memory T cell phenotype. Upon stimulation, these cell lines and clones secreted a Th2-like cytokine profile. The Dsg3 responses of these T cells were restricted to HLA-DR, and not -DQ and -DP, of the major histocompatibility complex. This information will help to elucidate the cellular immune abnormalities leading to production of pathogenic IgG autoantibodies in patients with PV.