Jones H P, Hodge L M, Fujihashi K, Kiyono H, McGhee J R, Simecka J W
Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
J Immunol. 2001 Oct 15;167(8):4518-26. doi: 10.4049/jimmunol.167.8.4518.
The purpose of this study was to determine the nature of the CD4(+) Th cell responses induced after nasal-pulmonary immunization, especially those coinciding with previously described pulmonary inflammation associated with the use of the mucosal adjuvant, cholera toxin (CT). The major T cell population in the lungs of naive mice was CD4(+), and these cells were shown to be predominantly of Th2 type as in vitro polyclonal stimulation resulted in IL-4, but not IFN-gamma, production. After nasal immunization with influenza Ag alone, Th2 cytokine mRNA (IL-4 and IL-5) levels were increased, whereas there was no change in Th1 cytokine (IL-2 and IFN-gamma) mRNA expression. The use of the mucosal adjuvant, CT, markedly enhanced pulmonary Th2-type responses; however, there was also a Th1 component to the T cell response. Using in vitro Ag stimulation of pulmonary lymphocytes, influenza virus-specific cytokine production correlated with the mRNA cytokine results. Furthermore, there was a large increase in CD4(+) Th cell numbers in lungs after nasal immunization using CT, correlating with the pulmonary inflammatory infiltrate previously described. Coincidentally, both macrophage-inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta mRNA expression increased in the lungs after immunization with Ag plus CT, while only MIP-1beta expression increased when mice were given influenza Ag alone. Our study suggests a mechanism to foster Th1 cell recruitment into the lung, which may impact on pulmonary immune responses. Thus, while Th2 cell responses may be prevalent in modulating mucosal immunity in the lungs, Th1 cell responses contribute to pulmonary defenses during instances of intense immune stimulation.
本研究的目的是确定经鼻-肺免疫后诱导的CD4(+) Th细胞反应的性质,尤其是那些与先前描述的使用黏膜佐剂霍乱毒素(CT)相关的肺部炎症同时发生的反应。未免疫小鼠肺中的主要T细胞群体是CD4(+),体外多克隆刺激结果显示这些细胞主要为Th2型,因为会产生IL-4而非IFN-γ。单独用流感抗原经鼻免疫后,Th2细胞因子mRNA(IL-4和IL-5)水平升高,而Th1细胞因子(IL-2和IFN-γ)mRNA表达无变化。黏膜佐剂CT的使用显著增强了肺部Th2型反应;然而,T细胞反应中也存在Th1成分。通过体外对肺淋巴细胞进行抗原刺激,流感病毒特异性细胞因子产生情况与mRNA细胞因子结果相关。此外,使用CT经鼻免疫后肺中CD4(+) Th细胞数量大幅增加,这与先前描述的肺部炎性浸润相关。巧合的是,用抗原加CT免疫后肺中巨噬细胞炎性蛋白-1α(MIP-1α)和MIP-1β mRNA表达均增加,而单独给小鼠注射流感抗原时只有MIP-1β表达增加。我们的研究提示了一种促进Th1细胞募集到肺中的机制,这可能会影响肺部免疫反应。因此,虽然Th2细胞反应可能在调节肺部黏膜免疫中普遍存在,但在强烈免疫刺激情况下,Th1细胞反应有助于肺部防御。