Increased Host Resistance against Pneumocystis carinii Pneumonia in γδ T-Cell-Deficient Mice: Protective Role of Gamma Interferon and CD8+ T Cells
Increased Host Resistance against Pneumocystis carinii Pneumonia in γδ T-Cell-Deficient Mice: Protective Role of Gamma Interferon and CD8+ T Cells
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γδ T 细胞缺陷小鼠宿主对卡氏肺孢子虫肺炎的抵抗力增强：γ 干扰素和 CD8+ T 细胞的保护作用
作者：
C. Steele;M. Zheng;E. Young;L. Marrero;J. Shellito;J. Kolls
摘要虽然αβT细胞受体阳性(αβ-TCR+)T细胞与卡氏肺孢子虫感染的易感性之间存在明确的关系，但其他T细胞亚群的作用尚不清楚。以前的研究表明，在卡氏肺孢子虫肺炎期间，γδ-TcR+T细胞渗入肺内。因此，本研究探讨了γδ-TcR+T细胞在卡氏肺孢子虫肺炎宿主防御中的作用。C57BL/6(对照组)和B6.129P2-Tcrdtm1Ma(γδ-Tcr+T细胞缺陷)小鼠气管内接种卡氏肺孢子虫。在特定的时间点，处死小鼠，分析卡氏肺孢子虫的负荷、T细胞亚群和肺组织中的细胞因子水平。对卡氏肺孢子虫感染负荷的分析表明，γδ-Tcr+T细胞缺陷小鼠的感染比C57BL/6对照组的感染更快、更彻底地消失。这种分辨率的提高与主要由CD8+T细胞产生的支气管肺泡灌洗液中的干扰素(γ)水平升高以及CD8+T细胞的招募增加有关。在单独的实验中，中和干扰素-γ或在感染早期耗尽CD8+T细胞，取消了以前在γδ-TCR+T细胞缺陷小鼠中观察到的增强的分辨率。这些结果表明γδ-TcR+T细胞的存在通过与肺CD8+T细胞的相互作用和组织产生干扰素-γ来调节宿主对卡氏肺孢子虫肺炎的易感性。
ABSTRACT Although a clear relationship between αβ T-cell receptor-positive (αβ-TCR+) CD4+ T cells and susceptibility to Pneumocystis carinii infection exists, the role of other T-cell subsets is less clearly defined. Previous studies have shown that γδ-TCR+ T cells infiltrate into the lung during P. carinii pneumonia. Therefore, the present study examined the role of γδ-TCR+ T cells in host defense against P. carinii pneumonia. C57BL/6 (control) and B6.129P2-Tcrdtm1Mom (γδ-TCR+ T-cell-deficient) mice were inoculated intratracheally with P. carinii. At specific time points, mice were sacrificed and analyzed for P. carinii burden, T-cell subsets, and cytokine levels in lung tissue. Analysis of P. carinii burden showed a more rapid and complete resolution of infection in γδ-TCR+ T-cell-deficient mice than in C57BL/6 controls. This augmented resolution was associated with elevated gamma interferon (IFN-γ) levels in bronchoalveolar lavage fluid predominantly produced by CD8+ T cells, as well as an increased recruitment of CD8+ T cells in general. In separate experiments, neutralization of IFN-γ or depletion of CD8+ T cells early during infection abolished the augmented resolution previously observed in γδ-TCR+ T-cell-deficient mice. These results show that the presence of γδ-TCR+ T cells modulates host susceptibility to P. carinii pneumonia through interactions with pulmonary CD8+ T cells and tissue production of IFN-γ.
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改变肺部宿主防御的基因疗法。
DOI：
10.1053/srin.2001.22725
发表时间：
2001
期刊：
Seminars in respiratory infections
影响因子：
--
作者：
Kolls,JK;Ye,P;Shellito,JE
通讯作者：
Shellito,JE
影响因子：
15.9
作者：
Zheng, MQ;Shellito, JE;Kolls, JK
通讯作者：
Kolls, JK
小鼠急性弓形虫感染期间 γδ T 细胞的诱导。
DOI：
--
发表时间：
1996
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kasper,LH;Matsuura,T;Fonseka,S;Arruda,J;Channon,JY;Khan,IA
通讯作者：
Khan,IA
在 CD4 T 细胞耗尽的小鼠中，IFN-γ 和 CD8 T 细胞可恢复宿主对卡氏肺孢子虫的防御能力。
DOI：
--
发表时间：
1999
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kolls,JK;Habetz,S;Shean,MK;Vazquez,C;Brown,JA;Lei,D;Schwarzenberger,P;Ye,P;Nelson,S;Summer,WR;Shellito,JE
通讯作者：
Shellito,JE
影响因子：
158.5
作者：
PHAIR, J;MUNOZ, A;SAAH, A
通讯作者：
SAAH, A