Early delayed-type hypersensitivity eosinophil infiltrates depend on T helper 2 cytokines and interferon-γ via CXCR3 chemokines
Early delayed-type hypersensitivity eosinophil infiltrates depend on T helper 2 cytokines and interferon-γ via CXCR3 chemokines
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DOI：
10.1111/j.0019-2805.2004.01818.x
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发表时间：
2004-03-01
期刊：
影响因子：
6.4
通讯作者：
Askenase, PW
中科院分区：
文献类型：
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作者：
Akahira-Azuma, M;Szczepanik, M;Askenase, PW
我们研究了辅助性T细胞（Th）1型和Th 2型细胞因子在免疫后早期引起的可溶性蛋白抗原的迟发型超敏反应中的作用。通过皮内注射无佐剂或皮下注射完全弗氏佐剂致敏小鼠，随后皮内耳攻击。在第3天，野生型小鼠中引起了抗原特异性嗜酸性粒细胞丰富的反应，但在没有佐剂的T细胞受体α（-/-）小鼠中没有。用抗原刺激的引流淋巴结T细胞分泌白细胞介素（IL）-4、IL-5和干扰素-γ（IFN-γ）。还产生IFN-γ依赖性特异性免疫球蛋白G（IgG）2a和IL-4依赖性IgG 1。在IL-5（-/-）、IL-4（-/-）和信号转导和转录激活因子-6（STAT-6）（-/-）小鼠中，以及在野生型小鼠中进行抗IL-4治疗后，迟发型超敏反应性耳肿胀和局部嗜酸性粒细胞募集减少，表明Th 2机制。有趣的是，IFN-γ（-/-）小鼠的反应也降低，IFN-γ蛋白和IFN-γ诱导的CXC趋化因子IP-10存在于24小时耳组织提取物中，表明Th 1效应。最后，在缺乏CXCR 3（IP-10的趋化因子受体）的小鼠中，耳肿胀、总组织学和嗜酸性粒细胞减少。这些结果表明，在早期迟发型超敏反应中，Th 2样（IL-5、IL-4和STAT-6）和Th 1样（IFN-γ、IP-10、CXCR 3）途径均有助于嗜酸性粒细胞的募集。
We investigated the role of T helper (Th)1- and Th2-type cytokines in delayed-type hypersensitivity to soluble protein antigens elicited early postimmunization. Mice were sensitized by intradermal injection without adjuvants, or subcutaneously with complete Freund's adjuvant, and subsequently ear challenged intradermally. As soon as day 3, antigen-specific eosinophil-rich responses were elicited in wild-type mice, but not in T-cell receptor-alpha(-/-) mice without adjuvant. Draining lymph node T cells stimulated with antigen secreted interleukin (IL)-4, IL-5 and interferon-gamma (IFN-gamma). IFN-gamma-dependent specific immunoglobulin G (IgG)2a and IL-4-dependent IgG1 were also generated. Delayed-type hypersensitivity ear swelling and local eosinophil recruitment were decreased in IL-5(-/-), IL-4(-/-) and signal transducer and activator of transcription-6 (STAT-6)(-/-) mice, and with anti-IL-4 treatment of wild-type mice, suggesting Th2 mechanisms. Interestingly, responses were also decreased in IFN-gamma(-/-) mice, and IFN-gamma protein and the IFN-gamma-inducible CXC chemokine, IP-10, were present in 24-hr ear tissue extracts, suggesting Th1 effects. Finally, ear swelling, total histology and eosinophils were decreased in mice deficient in CXCR3, the chemokine receptor for IP-10. These results suggest that both a Th2-like (IL-5, IL-4 and STAT-6) and a Th1-like (IFN-gamma, IP-10, CXCR3) pathway contribute to eosinophil recruitment in early delayed-type hypersensitivity.