Engeman Tara, Gorbachev Anton V, Kish Danielle D, Fairchild Robert L
Department of Immunology, The Cleveland Clinic Foundation, Ohio, USA.
J Leukoc Biol. 2004 Nov;76(5):941-9. doi: 10.1189/jlb.0304193. Epub 2004 Aug 24.
Recruitment of antigen-specific T cells into the skin is a critical initiating event during immune responses to many parasites and tumors as well as T cell-mediated, cutaneous, allergic responses and autoimmune diseases. Mechanisms directing T cell trafficking into skin remain largely undefined. Here, we show that cutaneous contact with reactive antigen induces KC/CXC chemokine ligand 1 production and neutrophil infiltration in an antigen, dose-dependent manner. The intensity of neutrophil infiltration into cutaneous antigen challenge sites, in turn, controls the number of antigen-primed T cells recruited into the site and the magnitude of the immune response elicited. The absence of responses in immune animals challenged with suboptimal doses of antigen is overcome by manipulating neutrophil infiltration that then directs antigen-primed T cell infiltration into the challenge site. This inflammation also directs T cells primed to one antigen (dinitrofluorobenzene) into the site when challenged with a completely different antigen (oxazolone). These results identify the intensity of neutrophil infiltration into cutaneous, antigen-deposition sites as a critical parameter for the level of antigen-primed T cell recruitment to mediate the adaptive immune response. This interplay between the innate and adaptive responses suggests a strategy to modulate, in a positive or negative manner, antigen-primed T cell infiltration into cutaneous inflammation sites.
在针对许多寄生虫、肿瘤以及T细胞介导的皮肤过敏反应和自身免疫性疾病的免疫反应过程中，抗原特异性T细胞募集至皮肤是一个关键的起始事件。引导T细胞向皮肤迁移的机制在很大程度上仍不明确。在此，我们表明皮肤与反应性抗原接触会以抗原剂量依赖性方式诱导角质形成细胞/ CXC趋化因子配体1的产生和中性粒细胞浸润。反过来，中性粒细胞浸润至皮肤抗原攻击部位的强度控制着募集至该部位的抗原致敏T细胞数量以及所引发免疫反应的强度。用次优剂量抗原攻击免疫动物时缺乏反应的情况可通过操控中性粒细胞浸润得以克服，而中性粒细胞浸润随后会引导抗原致敏T细胞浸润至攻击部位。当用完全不同的抗原（恶唑酮）攻击时，这种炎症反应还会将针对一种抗原（二硝基氟苯）致敏的T细胞引导至该部位。这些结果确定了中性粒细胞浸润至皮肤抗原沉积部位的强度是介导适应性免疫反应的抗原致敏T细胞募集水平的关键参数。先天性和适应性反应之间的这种相互作用提示了一种以正向或负向方式调节抗原致敏T细胞浸润至皮肤炎症部位的策略。
