Zöller Margot, McElwee Kevin J, Vitacolonna Mario, Hoffmann Rolf
Department of Tumor Progression and Tumor Defense, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
J Autoimmun. 2004 Nov;23(3):241-56. doi: 10.1016/j.jaut.2004.08.002.
Alopecia areata (AA) is a putative, cell-mediated autoimmune disease of anagen stage hair follicles. Inter- and intra-follicular lymphocytic infiltrates are associated with alopecia that may progress from an initially patchy presentation to extensive, even universal, hair loss. We previously noted in a mouse model of AA that regulatory T cells (Treg) are absent from draining lymph nodes and that expression of CD44v7 is transiently upregulated. Both features might explain autoreactive T cell persistence. Here we explored whether similar changes are seen in AA patients' peripheral blood mononuclear cells (PBMC). There was no clear evidence for a reduction in Treg as a possible means to support sustained T cell activation. However, progressive AA patients' PBMC displayed increased resistance towards apoptosis, which was accompanied by a decrease in CD95L+ and an increase in CD44v7+ cells. Notably, an expanded population of CD4+CD25+CD154+ T cells in progressive AA patients' PBMC was apoptosis resistant and expressed CD44v7. Thus, survival of activated T cells in progressive AA patients' PBMC is apparently sustained by downregulation of CD95L and upregulation of CD44v7 which is known to be associated with anti-apoptotic gene expression.
斑秃(AA)是一种推测的、细胞介导的生长期毛囊自身免疫性疾病。毛囊间和毛囊内淋巴细胞浸润与脱发相关,脱发可能从最初的斑片状发展为广泛的,甚至是全秃。我们之前在斑秃小鼠模型中发现,引流淋巴结中缺乏调节性T细胞(Treg),且CD44v7的表达短暂上调。这两个特征可能解释自身反应性T细胞的持续存在。在此,我们探讨了斑秃患者外周血单个核细胞(PBMC)中是否也有类似变化。没有明确证据表明Treg减少是支持T细胞持续活化的可能原因。然而,进展期斑秃患者的PBMC对凋亡的抵抗增加,同时伴有CD95L+细胞减少和CD44v7+细胞增加。值得注意的是,进展期斑秃患者PBMC中CD4+CD25+CD154+ T细胞的扩增群体具有抗凋亡能力并表达CD44v7。因此,进展期斑秃患者PBMC中活化T细胞的存活显然是通过CD95L的下调和CD44v7的上调来维持的,已知CD44v7与抗凋亡基因表达相关。