Suwandi Jessica S, Toes René E M, Nikolic Tatjana, Roep Bart O
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Clin Exp Rheumatol. 2015 Jul-Aug;33(4 Suppl 92):S97-103. Epub 2015 Oct 12.
Current immunosuppressive therapy acts systemically, causing collateral damage and does not necessarily cope with the cause of rheumatoid arthritis. Tissue specific immune modulation may restore tolerance in patients with autoimmune diseases such as RA, but desires knowledge on relevant target autoantigens. We present the case of type 1 diabetes as prototype autoimmune disease with established autoantigens to set the stage for tissue-specific immune modulation using tolerogenic dendritic cells pulsed with autoantigen in RA. This approach induces autoantigen-specific regulatory T cells that exert their tissue-specific action through a combination of linked suppression and infectious tolerance, introducing a legacy of targeted, localised immune regulation in the proximity of the lesion. Several trials are in progress in RA employing various types of tolerogenic DCs. With knowledge on mode of action and confounding effects of concomitant immunosuppressive therapy, this strategy may provide novel immune intervention that may also prevent RA in high-risk subjects.
当前的免疫抑制疗法是全身性作用，会造成附带损害，且不一定能应对类风湿性关节炎的病因。组织特异性免疫调节可能恢复自身免疫性疾病（如类风湿性关节炎）患者的耐受性，但需要了解相关的靶自身抗原。我们以1型糖尿病作为具有既定自身抗原的典型自身免疫性疾病为例，为在类风湿性关节炎中使用负载自身抗原的耐受性树突状细胞进行组织特异性免疫调节奠定基础。这种方法可诱导自身抗原特异性调节性T细胞，这些细胞通过连锁抑制和感染性耐受的组合发挥其组织特异性作用，在病变附近引入靶向、局部免疫调节的遗留效应。类风湿性关节炎的多项试验正在使用各种类型的耐受性树突状细胞进行。随着对作用模式以及伴随免疫抑制疗法的混杂效应的了解，这种策略可能提供新的免疫干预手段，也可能预防高危人群患类风湿性关节炎。
