The intensity of neutrophil infiltration controls the number of antigen-primed CD8 T cells recruited into cutaneous antigen challenge sites
The intensity of neutrophil infiltration controls the number of antigen-primed CD8 T cells recruited into cutaneous antigen challenge sites
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DOI：
10.1189/jlb.0304193
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发表时间：
2004-11-01
影响因子：
5.5
通讯作者：
Fairchid, RL
中科院分区：
文献类型：
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作者：
Engeman, T;Gorbachev, AV;Fairchid, RL
在许多寄生虫和肿瘤的免疫反应以及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中，抗原特异性T细胞在皮肤中的募集是一个关键的启动事件。引导T细胞进入皮肤的机制在很大程度上仍不清楚。在这里，我们表明，皮肤接触反应性抗原诱导KC/CXC趋化因子配体I的产生和中性粒细胞以抗原、剂量依赖的方式渗透。中性粒细胞渗入皮肤抗原攻击部位的强度反过来又控制着招募到抗原激发部位的T细胞的数量和所引发的免疫反应的大小。通过控制中性粒细胞的渗透，然后将抗原准备的T细胞渗透到攻击部位，可以克服免疫动物在受到次优剂量的抗原攻击时缺乏反应的问题。当受到完全不同的抗原(恶唑酮)攻击时，这种炎症也会引导与一种抗原(二硝基氟苯)结合的T细胞进入该部位。这些结果确定中性粒细胞渗入皮肤抗原沉积部位的强度是抗原刺激的T细胞募集水平的关键参数，以介导适应性免疫反应。这种先天反应和获得性反应之间的相互作用表明了一种以积极或消极的方式调节抗原诱导的T细胞渗透到皮肤炎症部位的策略。
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 antoimmune 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 I 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.