Tabeya Tetsuya, Yamamoto Motohisa, Naishiro Yasuyoshi, Ishigami Keisuke, Shimizu Yui, Yajima Hidetaka, Suzuki Chisako, Seki Nobuhiko, Takano Kenichi, Himi Tetsuo, Imai Kohzoh, Takahashi Hiroki, Shinomura Yasuhisa
Department of Internal Medicine, Dohkohkai Hospital , Sapporo, Hokkaido , Japan.
Mod Rheumatol. 2014 Nov;24(6):953-60. doi: 10.3109/14397595.2014.882045. Epub 2014 Mar 4.
Immunoglobulin (Ig) G4-related dacryoadenitis and sialadenitis, the so-called Mikulicz's disease (MD), is a chronic inflammatory disease. However, little is known about its pathogenesis and pathological condition. In the present study, we used immunohistological techniques to compare the roles of cytotoxic T lymphocytes (CTLs) in MD and primary Sjogren's syndrome (SS). We examined the state of CTLs [cytotoxic granule-positive rate and programmed death-1 (PD-1) expression rate] in the salivary glands.
The study samples comprised 12 submaxillary glands from untreated MD patients and 12 labial glands from SS patients. We performed immunofluorescence and multicolor immunofluorescence to stain CD8, perforin (PRF), granzyme B (GZMB), and PD-1. We measured the total number of CTLs as well as the PRF(+)CTLs, GZMB(+)CTLs, and PD-1(+)CTLs.
We found that the degree of infiltration of CTLs was equal in MD and SS, but the rate of CTLs with cytotoxic granules, especially PRF, in MD was less than in SS. In addition, the frequency of PD-1(+)CTLs in MD was higher than that in SS.
Cytotoxic granule-positive CTLs were in the minority in D salivary glands, and this regulation might relate to PD-1 signals like the state of exhaustion and anergy.
免疫球蛋白(Ig)G4相关泪腺炎和涎腺炎,即所谓的米库利奇病(MD),是一种慢性炎症性疾病。然而,对其发病机制和病理状况知之甚少。在本研究中,我们使用免疫组织学技术比较细胞毒性T淋巴细胞(CTL)在MD和原发性干燥综合征(SS)中的作用。我们检查了涎腺中CTL的状态[细胞毒性颗粒阳性率和程序性死亡-1(PD-1)表达率]。
研究样本包括12例未经治疗的MD患者的颌下腺和12例SS患者的唇腺。我们进行了免疫荧光和多色免疫荧光以对CD8、穿孔素(PRF)、颗粒酶B(GZMB)和PD-1进行染色。我们测量了CTL的总数以及PRF(+)CTL、GZMB(+)CTL和PD-1(+)CTL的数量。
我们发现MD和SS中CTL的浸润程度相同,但MD中具有细胞毒性颗粒的CTL比例,尤其是PRF,低于SS。此外,MD中PD-1(+)CTL的频率高于SS。
细胞毒性颗粒阳性CTL在涎腺中占少数,这种调节可能与PD-1信号有关,如耗竭和无反应状态。