Akahira-Azuma Moe, Szczepanik Marian, Tsuji Ryohei F, Campos Regis A, Itakura Atsuko, Mobini Narciss, McNiff Jennifer, Kawikova Ivana, Lu Bao, Gerard Craig, Pober Jordan S, Askenase Philip W
Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-0813, USA.
Immunology. 2004 Mar;111(3):306-17. doi: 10.1111/j.0019-2805.2004.01818.x.
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.
我们研究了辅助性T细胞（Th）1型和Th2型细胞因子在免疫接种后早期引发的对可溶性蛋白抗原的迟发型超敏反应中的作用。通过无佐剂皮内注射或用完全弗氏佐剂皮下注射使小鼠致敏，随后进行皮内耳部攻击。早在第3天，野生型小鼠就引发了抗原特异性富含嗜酸性粒细胞的反应，但在无佐剂的T细胞受体α基因敲除小鼠中未引发。用抗原刺激引流淋巴结T细胞可分泌白细胞介素（IL）-4、IL-5和干扰素-γ（IFN-γ）。还产生了IFN-γ依赖的特异性免疫球蛋白G（IgG）2a和IL-4依赖的IgG1。在IL-5基因敲除、IL-4基因敲除和信号转导及转录激活因子6（STAT-6）基因敲除小鼠中，以及用抗IL-4处理野生型小鼠后，迟发型超敏反应耳部肿胀和局部嗜酸性粒细胞募集减少，提示存在Th2机制。有趣的是，IFN-γ基因敲除小鼠的反应也减少，并且在24小时耳部组织提取物中存在IFN-γ蛋白和IFN-γ诱导的CXC趋化因子IP-10，提示存在Th1效应。最后，在缺乏IP-10趋化因子受体CXCR3的小鼠中，耳部肿胀、整体组织学和嗜酸性粒细胞减少。这些结果表明，类似Th2（IL-5、IL-4和STAT-6）和类似Th1（IFN-γ、IP-10、CXCR3）的途径均有助于早期迟发型超敏反应中嗜酸性粒细胞的募集。
