Pender Michael P
School of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia.
Autoimmune Dis. 2012;2012:189096. doi: 10.1155/2012/189096. Epub 2012 Jan 24.
CD8+ T-cell deficiency is a feature of many chronic autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, dermatomyositis, primary biliary cirrhosis, primary sclerosing cholangitis, ulcerative colitis, Crohn's disease, psoriasis, vitiligo, bullous pemphigoid, alopecia areata, idiopathic dilated cardiomyopathy, type 1 diabetes mellitus, Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, IgA nephropathy, membranous nephropathy, and pernicious anaemia. It also occurs in healthy blood relatives of patients with autoimmune diseases, suggesting it is genetically determined. Here it is proposed that this CD8+ T-cell deficiency underlies the development of chronic autoimmune diseases by impairing CD8+ T-cell control of Epstein-Barr virus (EBV) infection, with the result that EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells which would otherwise die in the target organ by activation-induced apoptosis. Autoimmunity is postulated to evolve in the following steps: (1) CD8+ T-cell deficiency, (2) primary EBV infection, (3) decreased CD8+ T-cell control of EBV, (4) increased EBV load and increased anti-EBV antibodies, (5) EBV infection in the target organ, (6) clonal expansion of EBV-infected autoreactive B cells in the target organ, (7) infiltration of autoreactive T cells into the target organ, and (8) development of ectopic lymphoid follicles in the target organ. It is also proposed that deprivation of sunlight and vitamin D at higher latitudes facilitates the development of autoimmune diseases by aggravating the CD8+ T-cell deficiency and thereby further impairing control of EBV. The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection.
CD8 + T细胞缺陷是许多慢性自身免疫性疾病的一个特征，包括多发性硬化症、类风湿性关节炎、系统性红斑狼疮、干燥综合征、系统性硬化症、皮肌炎、原发性胆汁性肝硬化、原发性硬化性胆管炎、溃疡性结肠炎、克罗恩病、银屑病、白癜风、大疱性类天疱疮、斑秃、特发性扩张型心肌病、1型糖尿病、格雷夫斯病、桥本甲状腺炎、重症肌无力、IgA肾病、膜性肾病和恶性贫血。它也出现在自身免疫性疾病患者的健康血亲中，这表明它是由基因决定的。本文提出，这种CD8 + T细胞缺陷通过损害CD8 + T细胞对爱泼斯坦 - 巴尔病毒（EBV）感染的控制，成为慢性自身免疫性疾病发展的基础，结果是EBV感染的自身反应性B细胞在靶器官中积累，在那里它们产生致病性自身抗体，并为自身反应性T细胞提供共刺激存活信号，否则这些T细胞会因激活诱导的凋亡而在靶器官中死亡。自身免疫被假定按以下步骤发展：（1）CD8 + T细胞缺陷，（2）原发性EBV感染，（3）CD8 + T细胞对EBV的控制降低，（4）EBV载量增加和抗EBV抗体增加，（5）靶器官中的EBV感染，（6）靶器官中EBV感染的自身反应性B细胞的克隆扩增，（7）自身反应性T细胞浸润到靶器官中，以及（8）靶器官中异位淋巴滤泡的形成。还提出，高纬度地区阳光和维生素D的缺乏通过加重CD8 + T细胞缺陷，从而进一步损害对EBV的控制，促进自身免疫性疾病的发展。该假说做出了可以检验的预测，包括通过控制EBV感染预防和成功治疗慢性自身免疫性疾病。
