Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Immunol Cell Biol. 2017 Sep;95(8):684-694. doi: 10.1038/icb.2017.38. Epub 2017 May 3.
Sjögren syndrome is an autoimmune disease characterized by targeted destruction of the lacrimal and salivary glands resulting in symptoms of severe ocular and oral dryness. Despite its prevalence, the mechanisms driving autoimmune manifestations are unclear. In patients and in the nonobese diabetic (NOD) mouse model of Sjögren syndrome, lymphocytic infiltrates consist of CD4 and CD8 T cells, although the role of CD8 T cells in disease pathogenesis has been largely unexplored. Here, we evaluated the contribution of CD8 T cells to lacrimal and salivary gland autoimmunity. Within the lacrimal and salivary glands of NOD mice, CD8 T cells were proliferating, expressed an activated phenotype, and produced inflammatory cytokines. Transfer of purified CD8 T cells isolated from the cervical lymph nodes (LNs) of NOD mice into NOD-severe combined immunodeficiency recipients resulted in inflammation of the lacrimal glands, but was not sufficient to cause inflammation of the salivary glands. Lacrimal gland-infiltrating CD8 T cells displayed a cytotoxic phenotype, and epithelial cell damage in the lacrimal glands was observed in recipients of CD8 T cells regardless of the presence of CD4 T cells. Collectively, our results demonstrate that CD8 T cells have a pathogenic role in lacrimal gland autoimmunity. The gland-specific pathogenicity of CD8 T cells makes them a valuable resource to further understand the mechanisms that discriminate lacrimal versus salivary gland autoimmunity and for the development of new therapeutics that target the early stages of disease.
干燥综合征是一种自身免疫性疾病，其特征是泪腺和唾液腺的靶向破坏，导致严重的眼部和口腔干燥症状。尽管其发病率较高，但驱动自身免疫表现的机制尚不清楚。在干燥综合征患者和非肥胖型糖尿病（NOD）小鼠模型中，淋巴细胞浸润由 CD4 和 CD8 T 细胞组成，尽管 CD8 T 细胞在疾病发病机制中的作用在很大程度上尚未得到探索。在这里，我们评估了 CD8 T 细胞对泪腺和唾液腺自身免疫的贡献。在 NOD 小鼠的泪腺和唾液腺中，CD8 T 细胞正在增殖，表达激活表型，并产生炎症细胞因子。从 NOD 小鼠的颈部淋巴结（LN）中分离出的纯化 CD8 T 细胞转移到 NOD-严重联合免疫缺陷（SCID）受者体内，导致泪腺炎症，但不足以引起唾液腺炎症。泪腺浸润的 CD8 T 细胞表现出细胞毒性表型，并且无论是否存在 CD4 T 细胞，在接受 CD8 T 细胞的受者中都观察到泪腺上皮细胞损伤。总之，我们的结果表明 CD8 T 细胞在泪腺自身免疫中具有致病性作用。CD8 T 细胞的腺体特异性致病性使它们成为进一步了解区分泪腺与唾液腺自身免疫的机制以及开发针对疾病早期阶段的新疗法的有价值资源。
