Autoantigen-Specific CD4+CD28low T Cell Subset Prevents Autoimmune Exocrinopathy in Murine Sjögren’s Syndrome1
Autoantigen-Specific CD4+CD28low T Cell Subset Prevents Autoimmune Exocrinopathy in Murine Sjögren’s Syndrome1
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自身抗原特异性 CD4+CD28low T 细胞亚群可预防小鼠干燥综合征的自身免疫性外分泌病1
作者：
K. Saegusa;N. Ishimaru;K. Yanagi;N. Haneji;Mizuho Nishino;M. Azuma;I. Saito;Y. Hayashi
出生后3天切除胸腺的NFS/sld突变小鼠中自发发生的类似于舍格伦综合征（SS）的器官特异性自身免疫性外分泌病依赖于Th 1型CD 4 + T细胞。我们先前报道了120-kDa α-胞衬蛋白的裂解产物可能是动物模型和患者SS发病机制中的重要自身抗原。我们证明，在一个动物模型的SS与明显的外分泌蛋白病，一个独特的CD 4 + T细胞亚群表达CD 28 low显着增加，在脾细胞发病前，但CD 4 + T细胞的患病小鼠几乎所有的CD 28 high。我们发现，在疾病发作前，这些小鼠的脾细胞显示出自身抗原特异性T细胞增殖的显着增加。对脾细胞体外细胞因子产生的分析表明，在疾病发作之前，动物模型中IL-2和IFN-γ的产生严重受损，而观察到高水平的IL-4。通过RT-PCR分析检测FACS分选的CD 4 + CD 28 low T细胞中细胞因子基因（包括IL-4、IL-10和TGF-β）的表达。将CD 4 + CD 28 low T细胞转移到动物模型中实际上阻止了自身免疫性病变的发展，包括自身抗体的产生。这些结果表明，一个CD 4 + CD 28 low T细胞亚群，是持续激活的器官特异性自身抗原可能发挥调节作用，在发展中的器官特异性自身免疫性疾病的动物模型的SS。
Organ-specific autoimmune exocrinopathy resembling Sjögren’s syndrome (SS) that spontaneously develops in NFS/sld mutant mice thymectomized 3 day after birth is dependent on Th1-type CD4+ T cells. We previously reported that a cleavage product of 120-kDa α-fodrin may be an important autoantigen in the pathogenesis of SS in both an animal model and the patients. We demonstrate that in an animal model of SS with overt exocrinopathy, a unique CD4+ T cell subset expressing CD28low is dramatically increased in spleen cells before the disease onset, but that the CD4+ T cells of diseased mice were virtually all CD28high. We found that the spleen cells in these mice before the disease onset showed a significant increase in autoantigen-specific T cell proliferation. Analysis of in vitro cytokine production by spleen cells indicated, before the disease onset, severely impaired production of IL-2 and IFN-γ in the animal model, whereas high levels of IL-4 were observed. Expression of cytokine genes, including IL-4, IL-10, and TGF-β, was detected in FACS-sorted CD4+CD28low T cells by RT-PCR analysis. Transfer of CD4+CD28low T cells into the animal model actually prevented the development of autoimmune lesions including autoantibody production. These results suggest that a CD4+CD28low T cell subset that is continuously activated by an organ-specific autoantigen may play a regulatory role in the development of organ-specific autoimmune disease in an animal model of SS.
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影响因子：
--
作者：
FOX, RI;ROBINSON, CA;HOWELL, FV
通讯作者：
HOWELL, FV
T 细胞耐受性受到 T 细胞对交叉反应性自肽的识别的影响。
DOI：
--
发表时间：
1996
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Tam,RC;Fedoseyeva,EV;Moskalenko,M;Garovoy,MR;Benichou,G
通讯作者：
Benichou,G
影响因子：
56.9
作者：
FRASER, JD;IRVING, BA;WEISS, A
通讯作者：
WEISS, A
影响因子：
4.4
作者：
P. Noel;L. Boise;J. Green;Craig B. Thompson
通讯作者：
P. Noel;L. Boise;J. Green;Craig B. Thompson
自身免疫的基础：第一部分。异常自我识别的机制。
DOI：
10.1016/0167-5699(95)80095-6
发表时间：
1995
期刊：
Immunology today.
影响因子：
--
作者：
Theofilopoulos,AN
通讯作者：
Theofilopoulos,AN