The Pulmonary Environment Promotes Th2 Cell Responses After Nasal-Pulmonary Immunization with Antigen Alone, but Th1 Responses Are Induced During Instances of Intense Immune Stimulation1
The Pulmonary Environment Promotes Th2 Cell Responses After Nasal-Pulmonary Immunization with Antigen Alone, but Th1 Responses Are Induced During Instances of Intense Immune Stimulation1
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仅使用抗原进行鼻肺免疫后，肺部环境会促进 Th2 细胞反应，但在强烈免疫刺激的情况下会诱导 Th1 细胞反应1
作者：
H. Jones;Lisa Hodge;K. Fujihashi;H. Kiyono;J. Mcghee;J. Simecka
本研究的目的是确定鼻-肺免疫后诱导的CD 4 + Th细胞应答的性质，特别是那些与先前描述的与使用粘膜佐剂霍乱毒素（CT）相关的肺部炎症相一致的应答。幼稚小鼠肺中的主要T细胞群是CD 4+，并且这些细胞显示主要是Th 2型，因为体外多克隆刺激导致IL-4而不是IFN-γ产生。单独用流感病毒抗原鼻腔免疫后，Th 2细胞因子mRNA（IL-4和IL-5）水平升高，而Th 1细胞因子（IL-2和IFN-γ）mRNA表达无变化。使用粘膜佐剂，CT，显着增强肺Th 2型反应，然而，也有一个Th 1的T细胞反应的组成部分。使用体外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，使用CT进行鼻免疫后，肺部CD 4 + Th细胞数量大幅增加，这与之前描述的肺部炎症浸润相关。巧合的是，巨噬细胞炎性蛋白-1 α（MIP-1α）和MIP-1β mRNA表达在用Ag + CT免疫小鼠后增加，而当仅给予流感病毒Ag时，只有MIP-1β表达增加。我们的研究提示了一种促进Th 1细胞募集到肺部的机制，这可能会影响肺部免疫反应。因此，虽然Th 2细胞应答在调节肺中的粘膜免疫中可能是普遍的，但Th 1细胞应答在强烈免疫刺激的情况下有助于肺防御。
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-γ, 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-γ) 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-1α (MIP-1α) and MIP-1β mRNA expression increased in the lungs after immunization with Ag plus CT, while only MIP-1β 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.
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影响因子：
4.4
作者：
M. Marinaro;H. Staats;T. Hiroi;R. Jackson;M. Coste;P. Boyaka;N. Okahashi;M. Yamamoto;Hiroshi Kiyono;Horst Bluethmann;K. Fujihashi;Jerry R. McGhee
通讯作者：
M. Marinaro;H. Staats;T. Hiroi;R. Jackson;M. Coste;P. Boyaka;N. Okahashi;M. Yamamoto;Hiroshi Kiyono;Horst Bluethmann;K. Fujihashi;Jerry R. McGhee
DOI：
10.1152/ajplung.2000.279.3.l592
发表时间：
2000-09-01
影响因子：
4.9
作者：
Dixon, AE;Mandac, JB;Clark, JG
通讯作者：
Clark, JG
影响因子：
4.4
作者：
K. B. Renegar;P. Small
通讯作者：
K. B. Renegar;P. Small
影响因子：
4.4
作者：
L. Cohn;J. Tepper;K. Bottomly
通讯作者：
L. Cohn;J. Tepper;K. Bottomly
DOI：
10.1073/pnas.89.15.6901
发表时间：
1992-08-01
影响因子：
11.1
作者：
MAZANEC, MB;KAETZEL, CS;NEDRUD, JG
通讯作者：
NEDRUD, JG