Strid Jessica, Callard Robin, Strobel Stephan
Immunobiology Unit, Institute of Child Health, University College London, UK.
Immunology. 2006 Sep;119(1):27-35. doi: 10.1111/j.1365-2567.2006.02401.x. Epub 2006 Jun 8.
Epicutaneous immunization is a potential novel technique for topical vaccine delivery. It targets the immunologically rich milieu of the skin while having the advantage of being a non-invasive immunization procedure. By disrupting the stratum corneum of the epidermis a natural adjuvant effect can be achieved through activation of resident Langerhans cells. This negates the normal need for co-application of noxious adjuvants. Epicutaneous immunization on barrier-disrupted skin induces potent antigen-specific systemic immunity with a strong T helper type 2 (Th2) bias. We show here that epicutaneous immunization enhances the vigour of a subsequent T-cell response to the same antigen. The induced systemic Th2 response prevents the development of Th1 responses induced through injection of antigen in complete Freund's adjuvant (CFA). Prior epicutaneous immunization results in reduced production of antigen-specific interferon-gamma and immunoglobulin G2a (IgG2a) and enhanced interleukin-4, IgG1 and IgE responses to immunization with CFA. Moreover, epicutaneous immunization converts an established Th1 response to a Th2 response, as demonstrated by the specific reduction of interferon-gamma and IgG2a and the enhancement of interleukin-4 and IgE. This Th2 dominance of epicutaneous immunization may have direct therapeutic application as an immune-modulating procedure in Th1-dominant diseases such as autoimmune rheumatoid arthritis, type 1 diabetes, Hashimoto's thyroiditis and multiple sclerosis.
表皮免疫是一种用于局部疫苗递送的潜在新技术。它针对皮肤中富含免疫细胞的微环境,同时具有非侵入性免疫程序的优势。通过破坏表皮角质层,可通过激活驻留的朗格汉斯细胞实现天然佐剂效应。这消除了通常对有害佐剂联合应用的需求。在屏障破坏的皮肤上进行表皮免疫可诱导强大的抗原特异性全身免疫,且具有强烈的2型辅助性T细胞(Th2)偏向。我们在此表明,表皮免疫可增强后续对相同抗原的T细胞反应的活力。诱导的全身Th2反应可防止通过在完全弗氏佐剂(CFA)中注射抗原诱导的Th1反应的发展。预先进行表皮免疫会导致抗原特异性干扰素-γ和免疫球蛋白G2a(IgG2a)的产生减少,并增强白细胞介素-4、IgG1和IgE对CFA免疫的反应。此外,表皮免疫可将已建立的Th1反应转变为Th2反应,这通过干扰素-γ和IgG2a的特异性减少以及白细胞介素-4和IgE的增强得以证明。表皮免疫的这种Th2优势可能作为一种免疫调节程序在Th1主导的疾病如自身免疫性类风湿性关节炎、1型糖尿病、桥本甲状腺炎和多发性硬化症中具有直接的治疗应用。