Hutchings P, O'Reilly L, Parish N M, Waldmann H, Cooke A
Department of Pathology, University of Cambridge, GB.
Eur J Immunol. 1992 Jul;22(7):1913-8. doi: 10.1002/eji.1830220735.
The use of immunosuppressive drugs in the management of autoimmunity penalizes a large part of the immune system for the misdemeanors of a small minority of T cells. An ideal form of therapy would be one in which it were possible to render the immune system tolerant of the inciting antigens with minimal effects on other responses. We here show that it is possible to re-establish self tolerance in an animal model of insulin-dependent diabetes mellitus without prior deletion of CD4+ T cells using a short course of therapy with a non-lytic monoclonal antibody to the CD4 adhesion receptor on T cells. This tolerance can be achieved even when diabetogenic cells are already in the pancreas. Primary responses to antigens given after therapy has ceased are normal and secondary responses to antigens seen prior to, but not during, the period of antibody therapy can remain unaffected. This suggests that intervention with selected CD4 antibodies may have significant advantages over and above that provided not only by conventional immunosuppression but also over that provided by a depleting antibody.
在自身免疫性疾病的治疗中使用免疫抑制药物会因少数T细胞的不当行为而损害大部分免疫系统。理想的治疗形式应该是能够使免疫系统对引发抗原产生耐受性，同时对其他反应影响最小。我们在此表明，在胰岛素依赖型糖尿病动物模型中，使用针对T细胞上CD4黏附受体的非溶细胞性单克隆抗体进行短期治疗，无需预先清除CD4 + T细胞，就有可能重新建立自身耐受性。即使致糖尿病细胞已存在于胰腺中，也能实现这种耐受性。治疗停止后给予抗原的初次反应正常，抗体治疗期间之前但不是治疗期间所见抗原的二次反应可能不受影响。这表明，与传统免疫抑制以及耗竭性抗体相比，使用选定的CD4抗体进行干预可能具有显著优势。
