The pulmonary environment promotes Th2 cell responses after nasal-pulmonary immunization with antigen alone, but Th1 responses are induced during instances of intense immune stimulation
The pulmonary environment promotes Th2 cell responses after nasal-pulmonary immunization with antigen alone, but Th1 responses are induced during instances of intense immune stimulation
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DOI：
10.4049/jimmunol.167.8.4518
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发表时间：
2001-10-15
影响因子：
4.4
通讯作者：
Simecka, JW
中科院分区：
文献类型：
--
作者：
Jones, HP;Hodge, LM;Simecka, JW
这项研究的目的是确定鼻 - 肺免疫后诱导的CD4（+）细胞反应的性质，尤其是那些与先前描述的肺，与使用粘膜佐剂，霍乱毒素（CT）相关的炎症。幼稚小鼠肺中的主要T细胞群为CD4+，这些细胞被证明是Th2类型的体外多克隆刺激，导致IL-4产生IL-4，但不是IFN-GAMMA的产生。单独使用流感Ag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-GAMMA）mRNA表达没有变化。粘膜佐剂CT的使用显着增强了肺Th2型反应；但是，T细胞反应也有Th1分量。利用体外AG刺激肺淋巴细胞，流感病毒特异性细胞因子的产生与mRNA细胞因子结果相关。此外，鼻腔免疫后使用CT，CD4（+）TH细胞数量大大增加，与先前描述的肺炎症性浸润相关。偶然地，巨噬细胞炎症蛋白-1α（MIP-1α）和MIP-1βmRNA表达在用Ag Plus CT免疫后，肺中的肺部表达增加了，而仅当单独给予流感流感的Ag时，仅MIP-1β表达增加。我们的研究提出了一种将Th1细胞募集到肺部的机制，这可能会影响肺免疫反应。因此，尽管TH2细胞反应可能在调节肺部粘膜免疫方面普遍存在，但在强烈的免疫刺激实例中，Th1细胞反应有助于肺部防御。
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-1 alpha (MIP-1 alpha) and MIP-1 beta mRNA expression increased in the lungs after immunization with Ag plus CT, while only MIP-1 beta 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.