Zeher M, Szodoray P, Gyimesi E, Szondy Z
University Medical School of Debrecen, Hungary.
Arthritis Rheum. 1999 Aug;42(8):1673-81. doi: 10.1002/1529-0131(199908)42:8<1673::AID-ANR16>3.0.CO;2-1.
To investigate whether a change in the CD95-related apoptosis of T lymphocytes might have a share in the development of the disease in patients with primary Sjögren's syndrome (SS).
Two-color cytometric analysis was used to study the phenotype of freshly separated mononuclear cells, while Western blotting was used to detect CD95 ligand (CD95L) expression in total homogenates of isolated CD4+ T lymphocytes. The ability of various subpopulations of T cells to undergo apoptosis was investigated in 1-day cultures in medium alone or following various (anti-CD3, anti-CD95 monoclonal antibody, calcium ionophore) treatments. Apoptosis was detected using 7-aminoactinomycin D dye.
Compared with the findings in healthy controls, the number of CD4+ T lymphocytes was decreased, while their expression of CD95, HLA-DR, and CD45RO was significantly increased in patients with primary SS. A positive correlation was found between the activity of disease, the decrease in the CD4+ T cell number, and the increase in the expression of CD95, CD95L, HLA-DR, and CD45RO molecules within the CD4+ T cell subset. An increased rate of spontaneous, anti-CD3-, or anti-CD95-induced apoptosis was found in the T cells of SS patients, and this was more pronounced in the CD4+ T cell population, correlated with the decreased CD4+ T cell number, increased CD45RO expression, and activity of disease, and concerned mainly the CD95+ cells.
These observations indicate that the increased susceptibility to apoptosis of peripheral CD4+ T cells from SS patients correlates with disease activity. These findings support the hypothesis that the chronic activation of the immune system that occurs in this autoimmune disease is the primary mechanism responsible for this cell-deletion process.
探讨原发性干燥综合征（SS）患者T淋巴细胞中与CD95相关的细胞凋亡变化是否参与了疾病的发生发展。
采用双色细胞仪分析新鲜分离的单核细胞表型，同时用蛋白质印迹法检测分离的CD4⁺T淋巴细胞总匀浆中CD95配体（CD95L）的表达。在单独培养基中培养1天或经各种（抗CD3、抗CD95单克隆抗体、钙离子载体）处理后，研究T细胞各亚群的凋亡能力。使用7-氨基放线菌素D染料检测细胞凋亡。
与健康对照相比，原发性SS患者CD4⁺T淋巴细胞数量减少，而其CD95、HLA-DR和CD45RO的表达显著增加。在原发性SS患者中，疾病活动度、CD4⁺T细胞数量减少以及CD4⁺T细胞亚群内CD95、CD95L、HLA-DR和CD45RO分子表达增加之间存在正相关。SS患者的T细胞中，自发、抗CD3或抗CD95诱导的凋亡率增加，在CD4⁺T细胞群体中更明显，与CD4⁺T细胞数量减少、CD45RO表达增加和疾病活动度相关，且主要涉及CD95⁺细胞。
这些观察结果表明，原发性SS患者外周CD4⁺T细胞对凋亡的易感性增加与疾病活动度相关。这些发现支持了这样的假说，即这种自身免疫性疾病中发生的免疫系统慢性激活是导致这种细胞缺失过程的主要机制。
