Roitt I M, Hutchings P R, Dawe K I, Sumar N, Bodman K B, Cooke A
Dept. of Immunology, University College & Middlesex School of Medicine, London, UK.
J Autoimmun. 1992 Apr;5 Suppl A:11-26. doi: 10.1016/0896-8411(92)90015-i.
There are two classes of autoimmune disease, organ-specific and non-organ specific or systemic. That cells producing autoantibodies are selected by antigen is strongly suggested by the presence of mutations and high affinity antibody. T-cells are pivotal in all forms of autoimmunity as evidenced by the therapeutic benefit of anti-T-cell monoclonals such as anti-CD4, and the frequent development of high affinity IgG autoantibodies. The production of anergic T-cells by the use of non-depleting anti-CD4 in the presence of antigen is discussed with particular reference to its potential for immunological intervention in autoimmune disease. It is possible to identify T-cell epitopes in organ-specific autoimmunity using pathogenic T-cell clones or hybridomas to identify the peptide sequences which are reactive. Antigen-specific therapy may ultimately be based on such peptide epitopes. The specificity of the T-cells in systemic autoimmunity is still obscure, but there is some evidence that reactivity with certain germ-line idiotypes can lead to the development of systemic autoimmunity. The possibility of stimulating B-cells specific for auto-antigens such as DNA becomes feasible if a complex of antibody and DNA is taken up by these specific B-cells and processed idiotype is presented to T-helpers specific for those idiotype epitopes. Evidence is presented that there may be pre-existing defects in the target organ in certain organ-specific disorders, and the evidence for a glycosylation defect in the IgG in patients with rheumatoid arthritis is explored. It is noted that the spouses of probands with rheumatoid arthritis is explored. It is noted that the spouses of probands with rheumatoid arthritis also tend to have this glycosylation defect and this raises the possibility of an effect due to an environmental factor, such as a microbial infection. Molecular mimicry of autoantigens by microbes can stimulate autoreactive cells by their cross-reactivity. It is emphasized that cross-reaction which gives rise to the priming of autoreactive T-cells could give rise to the establishment of a chronic autoimmune state. In animals with normal regulatory immune systems, such induced autoimmunity is ultimately corrected and it is only in animals where there are defects in regulation, that autoimmunity persists. Thus, there are many factors giving rise to autoimmunity, and the diseases are rightly regarded as multifactorial in origin.
自身免疫性疾病可分为两类，即器官特异性和非器官特异性或全身性。产生自身抗体的细胞是由抗原选择的，这一点从突变和高亲和力抗体的存在中得到了有力提示。T细胞在所有形式的自身免疫中都起着关键作用，抗CD4等抗T细胞单克隆抗体的治疗益处以及高亲和力IgG自身抗体的频繁产生都证明了这一点。本文讨论了在有抗原存在的情况下使用非清除性抗CD4产生无反应性T细胞，特别提及了其在自身免疫性疾病免疫干预方面的潜力。利用致病性T细胞克隆或杂交瘤来鉴定反应性肽序列，从而在器官特异性自身免疫中识别T细胞表位是可行的。抗原特异性治疗最终可能基于此类肽表位。全身性自身免疫中T细胞的特异性仍不清楚，但有证据表明与某些种系独特型的反应性可导致全身性自身免疫的发展。如果抗体和DNA复合物被这些特异性B细胞摄取并将加工后的独特型呈递给针对那些独特型表位的T辅助细胞，那么刺激针对自身抗原（如DNA）的B细胞就变得可行。有证据表明，在某些器官特异性疾病中，靶器官可能预先存在缺陷，并探讨了类风湿性关节炎患者IgG中糖基化缺陷的证据。值得注意的是，本文探讨了类风湿性关节炎先证者的配偶情况。值得注意的是，类风湿性关节炎先证者的配偶也往往存在这种糖基化缺陷，这增加了环境因素（如微生物感染）产生影响的可能性。微生物对自身抗原的分子模拟可通过其交叉反应性刺激自身反应性细胞。需要强调的是，引发自身反应性T细胞致敏的交叉反应可能导致慢性自身免疫状态的建立。在具有正常调节免疫系统的动物中，这种诱导的自身免疫最终会得到纠正，只有在调节存在缺陷的动物中，自身免疫才会持续存在。因此，导致自身免疫的因素有很多，这些疾病被正确地认为是多因素起源的。
