Ozaki Y, Amakawa R, Ito T, Iwai H, Tajima K, Uehira K, Kagawa H, Uemura Y, Yamashita T, Fukuhara S
Kansai Medical University, Moriguchi, Osaka, Japan.
Arthritis Rheum. 2001 Feb;44(2):419-31. doi: 10.1002/1529-0131(200102)44:2<419::AID-ANR61>3.0.CO;2-U.
We recently identified 3 fractions of human peripheral blood (PB) dendritic cells (DC), including the monocyte-associated fractions 1 and 2 (CD1a+,CD11c+ and CD1a-,CD11c+, respectively) and the lymphoid-associated fraction 3 (CD1a-,CD11c-). We attempted to determine whether these fractions were altered in Sjögren's syndrome (SS).
We examined 23 patients with primary SS and 22 normal control subjects. DC were purified from PB and analyzed by flow cytometry. Immunohistochemical staining of labial salivary glands of SS patients was performed with monoclonal antibodies against fascin, which is known to be specific for DC.
The total numbers of PB DC and fraction 1 DC were decreased in SS. Immunohistochemical staining demonstrated that fascin+,CD11c+,HLA-DR+ mononuclear cells were present and scattered among numerous fascin-hyperfiltrating cells in SS patients. Interferon-gamma (IFNgamma)-producing Th1 cells were shown to be increased in both PB and salivary glands of patients, indicating the presence of general IFNgamma-producing Th1 polarization in SS. Furthermore, numbers of Thl cells were increased when naive T cells were cocultured with fraction 1 DC in vitro.
These findings suggest selective trafficking of fraction 1 DC into focal sites of inflammation and subsequent promotion of Th1 balance, suggesting a novel pathogenesis of SS.
我们最近鉴定出人类外周血（PB）树突状细胞（DC）的3个亚群，包括与单核细胞相关的亚群1和亚群2（分别为CD1a +、CD11c +和CD1a -、CD11c +）以及与淋巴细胞相关的亚群3（CD1a -、CD11c -）。我们试图确定这些亚群在干燥综合征（SS）中是否发生改变。
我们检查了23例原发性SS患者和22名正常对照者。从PB中纯化DC，并通过流式细胞术进行分析。用已知对DC具有特异性的抗fascin单克隆抗体对SS患者的唇唾液腺进行免疫组织化学染色。
SS患者PB DC和亚群1 DC的总数减少。免疫组织化学染色显示，fascin +、CD11c +、HLA - DR +单核细胞存在于SS患者众多fascin高表达细胞中并呈散在分布。结果显示，患者PB和唾液腺中产生干扰素-γ（IFNγ）的Th1细胞均增加，表明SS中存在全身性产生IFNγ的Th1极化。此外，当体外将未活化T细胞与亚群1 DC共培养时，Th1细胞数量增加。
这些发现提示亚群1 DC选择性迁移至炎症灶并随后促进Th1平衡，提示SS存在新的发病机制。
