T lymphocytes from a subset of patients with pemphigus vulgaris respond to both desmoglein-3 and desmoglein-1.
T lymphocytes from a subset of patients with pemphigus vulgaris respond to both desmoglein-3 and desmoglein-1.
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部分寻常型天疱疮患者的 T 淋巴细胞对桥粒芯糖蛋白 3 和桥粒芯糖蛋白 1 均有反应。
DOI：
10.1111/1523-1747.ep12340738
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Diaz,LA
中科院分区：
文献类型：
--
作者：
Lin,MS;Swartz,SJ;Lopez,A;Ding,X;Fairley,JA;Diaz,LA
寻常型天疱疮和落叶型天疱疮是以上皮内水疱和抗桥粒糖蛋白自身抗体为特征的皮肤自身免疫性疾病。寻常型天疱疮和落叶型天疱疮自身抗体识别的抗原分别是桥粒芯糖蛋白-3（Dsg 3）和桥粒芯糖蛋白-1（Dsg 1）。Dsg 3和Dsg 1是细胞粘附分子的钙粘蛋白超基因家族的桥粒芯糖蛋白亚家族的成员。已经有充分的文献证明，寻常型天疱疮血清的一个子集对Dsg 1和Dsg 3都具有IgG反应性，这表明Dsg 1也可能参与这些患者的自身免疫应答。然而，在这些患者中T细胞自身免疫的细胞机制是完全未知的。在这项研究中，我们测试了8例寻常型天疱疮患者的T淋巴细胞与Dsg 3和Dsg 1融合蛋白孵育后的增殖反应。这些PV患者的血清中的四个显示与Dsg 1和Dsg 3的反应性，而其余四个仅与Dsg 3反应。我们发现，从那些表现出组合Dsg 1/Dsg 3自身抗体反应性的患者中获得的T细胞在暴露于Dsg 1或Dsg 3融合蛋白后显示出增殖反应。对这两种重组蛋白的细胞应答是高度特异性的，并且仅限于CD 4阳性T细胞群体。无抗Dsg 1血清反应性的寻常型天疱疮患者的T细胞对Dsg 3表现出增殖反应，但对Dsg 1没有反应。本研究中使用的Dsg 1融合蛋白与Dsg 3具有最小的序列同源性。因此，这项研究提供了第一个证据表明，寻常型天疱疮患者的一个子集的T细胞对Dsg 1和Dsg 3都有反应。
Pemphigus vulgaris and pemphigus foliaceus are cutaneous autoimmune diseases characterized by intraepithelial blisters and autoantibodies to desmosomal glycoproteins. The antigens recognized by pemphigus vulgaris and pemphigus foliaceus autoantibodies are desmoglein- 3 (Dsg3) and desmoglein-1 (Dsg1), respectively. Dsg3 and Dsg1 are members of the desmoglein subfamily of the cadherin supergene family of cell adhesion molecules. It has been well documented that a subset of pemphigus vulgaris sera have IgG reactivity to both Dsg1 and Dsg3, suggesting that Dsg1 may also participate in the autoimmune response of these patients. The cellular mechanisms of T cell autoimmunity in these patients, however, are completely unknown. In this study, we tested the proliferative responses of T lymphocytes from eight pemphigus vulgaris patients after incubation with Dsg3 and Dsg1 fusion proteins. The sera of four of these PV patients showed reactivity with both Dsg1 and Dsg3, whereas the remaining four reacted only with Dsg3. We found that T cells obtained from those patients that exhibited the combined Dsg1/Dsg3 autoantibody reactivity showed a proliferative response after exposure to either Dsg1 or Dsg3 fusion proteins. The cellular responses to both of these recombinant proteins were highly specific and restricted to the CD4-positive T cell population. T cells from pemphigus vulgaris patients with no anti-Dsg1 serum reactivity showed a proliferative response to Dsg3, but not to Dsg1. The Dsg1 fusion protein used in this study has minimal sequence homology with Dsg3. Thus, this study provides the first evidence that T cells from a subset of pemphigus vulgaris patients respond to both Dsg1 and Dsg3.