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小鼠中针对牙龈卟啉单胞菌的特异性T细胞细胞因子反应的遗传依赖性。

Genetic dependence of the specific T-cell cytokine response to Porphyromonas gingivalis in mice.

作者信息

Gemmell Erica, Carter Christine L, Bird Philip S, Seymour Gregory J

机构信息

Oral Biology and Pathology, School of Dentistry, The University of Queensland, Brisbane, Australia.

出版信息

J Periodontol. 2002 Jun;73(6):591-6. doi: 10.1902/jop.2002.73.6.591.

Abstract

BACKGROUND

Susceptibility to periodontal infections may, in part, be genetically determined. Porphyromonas gingivalis is a major periodontopathogen, and the immune response to this organism requires T-cell help. The aim of the present study was to examine the specific T-cell cytokine responses to P. gingivalis outer membrane antigens in a mouse model and their relationship with H-2 haplotype.

METHODS

BALB/c and DBA/2J (H-2d), CBACaH (H-2k), and C57BL6 (H-2b) mice were immunized with P. gingivalis outer membrane antigens weekly for 3 weeks. One week after the final injection, the spleens were removed, and 6 T-cell lines specific for P. gingivalis were established for each mouse strain. The percentage of CD4 and CD8 cells in the P. gingivalis-specific T-cell lines staining positive for intracytoplasmic interleukin (IL)-4, interferon (IFN)-gamma, and IL-10 was determined by 2-color flow cytometry.

RESULTS

The cytokine profiles of T-cell lines from BALB/c and DBA/2J mice showed no significant differences. Significantly fewer IL-4+, IFN-gamma+, and IL-10+ CD4 cells than IL-4+, IFN-gamma+, and IL-10+ CD8 cells, respectively, were demonstrated for both strains. P. gingivalis-specific T-cell lines generated from CBACaH mice were similar to those generated from BALB/c and DBA/2J mice; however, the mean percentage of IL-4+ CD4 cells in CBACaH mice was lower than the percentage of IFN-gamma+ CD4 cells. Also, the mean percentage of IFN-gamma+ CD4 cells in CBACaH mice was significantly increased compared to DBA/2J mice. Unlike the other 3 strains, T-cell lines established from C57BL6 mice contained similar percentages of cytokine-positive cells, although the percentage of IL-4+ CD4 cells was reduced in comparison to the percentage of CD8 cells. However, comparisons with the other 3 strains demonstrated a higher percentage of IL-4+ CD4 cells than in lines established from the spleens of DBA/2J mice, IFN-gamma+ CD4 cells than in lines established from BALB/c and CBACaH mice, and IL-10+ CD4 cells than in lines established from all 3 other strains. No significant differences in the percentage of positive CD8 cells were demonstrated between lines in the 4 strains of mice.

CONCLUSION

The specific T-cell response to P. gingivalis in mice may, in the case of the CD4 response, depend on MHC genes. These findings are consistent with the concept that patient susceptibility is important to the outcome of periodontal infection and may, in part, be genetically determined.

摘要

背景

对牙周感染的易感性可能部分由基因决定。牙龈卟啉单胞菌是一种主要的牙周病原体,对该菌的免疫反应需要T细胞的辅助。本研究的目的是在小鼠模型中检测对牙龈卟啉单胞菌外膜抗原的特异性T细胞细胞因子反应及其与H-2单倍型的关系。

方法

将BALB/c和DBA/2J(H-2d)、CBACaH(H-2k)及C57BL6(H-2b)小鼠每周用牙龈卟啉单胞菌外膜抗原免疫,共免疫3周。末次注射后1周,取出脾脏,为每个小鼠品系建立6个针对牙龈卟啉单胞菌的T细胞系。通过双色流式细胞术测定牙龈卟啉单胞菌特异性T细胞系中胞质内白细胞介素(IL)-4、干扰素(IFN)-γ和IL-10染色阳性的CD4和CD8细胞百分比。

结果

BALB/c和DBA/2J小鼠T细胞系的细胞因子谱无显著差异。两种品系中,IL-4+、IFN-γ+和IL-10+ CD4细胞分别显著少于IL-4+、IFN-γ+和IL-10+ CD8细胞。CBACaH小鼠产生的牙龈卟啉单胞菌特异性T细胞系与BALB/c和DBA/2J小鼠产生的相似;然而,CBACaH小鼠中IL-4+ CD4细胞的平均百分比低于IFN-γ+ CD4细胞的百分比。此外,与DBA/2J小鼠相比,CBACaH小鼠中IFN-γ+ CD4细胞的平均百分比显著增加。与其他3个品系不同,从C57BL6小鼠建立的T细胞系中细胞因子阳性细胞的百分比相似,尽管IL-4+ CD4细胞的百分比与CD8细胞相比有所降低。然而,与其他3个品系相比,C57BL6小鼠产生的IL-4+ CD4细胞百分比高于DBA/2J小鼠脾脏来源的细胞系,IFN-γ+ CD4细胞百分比高于BALB/c和CBACaH小鼠来源的细胞系,IL-10+ CD4细胞百分比高于其他所有3个品系来源的细胞系。4个小鼠品系的细胞系之间,阳性CD8细胞百分比无显著差异。

结论

在小鼠中,对牙龈卟啉单胞菌的特异性T细胞反应在CD4反应方面可能取决于MHC基因。这些发现与患者易感性对牙周感染结局很重要且可能部分由基因决定这一概念相符。

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