Okui T, Ito H, Honda T, Amanuma R, Yoshie H, Yamazaki K
Laboratory of Periodontology and Immunology, Department of Oral Health and Welfare, Niigata University Faculty of Dentistry, Niigata, Japan.
Oral Microbiol Immunol. 2008 Feb;23(1):49-54. doi: 10.1111/j.1399-302X.2007.00390.x.
Our previous study demonstrated that the gene expression of FOXP3, a characteristic marker for CD4(+) CD25(+) regulatory T cells in mice, is upregulated more in periodontitis than in gingivitis at the messenger RNA (mRNA) level. Furthermore, most of the T-cell clones established from periodontitis lesions expressed FOXP3 mRNA. However, role of the FOXP3(+) gingival T cells has not been elucidated.
The phenotype of FOXP3-expressing cells in periodontitis lesions was determined immunohistochemically. CD4(+) FOXP3(+) gingival T-cell clones were established from three patients with advanced periodontitis by using immunomagnetic beads. Gene expression and phenotype analyses were performed by reverse-transcription polymerase chain reactions and flow cytometry, respectively. The effect of CD4(+) FOXP3(+) T-cell clones on the proliferative response of CD4(+) CD25(-) T cells was examined by [(3)H]thymidine incorporation.
FOXP3 expression was found in some CD4(+) T cells and CD25(+) cells but not in CD8(+) T cells by immunohistochemistry. In spite of a substantial expression of the CD25 gene, the expression level of membrane CD25 on the CD4(+) FOXP3(+) gingival T-cell clones was low. While peripheral blood CD4(+) CD25(+) FOXP3(+) cells suppressed the proliferation of CD4(+) CD25(-) T cells, the CD4(+) CD25(low) FOXP3(+) gingival T-cell clones enhanced the proliferation significantly.
Our study makes it evident that most, if not all, of the FOXP3(+) T cells in periodontitis lesions can be considered to be effector T cells. The effector activity of the gingival T-cell clones could be attributable to the low level of membrane CD25 expression. Further studies are clearly needed to clarify the role of these T cells and their unique characteristics in the pathogenesis of periodontal disease.
我们之前的研究表明，FOXP3作为小鼠CD4(+) CD25(+)调节性T细胞的特征性标志物，在信使核糖核酸（mRNA）水平上，其基因表达在牙周炎中比在牙龈炎中上调得更多。此外，从牙周炎病变中建立的大多数T细胞克隆都表达FOXP3 mRNA。然而，FOXP3(+)牙龈T细胞的作用尚未阐明。
采用免疫组织化学方法确定牙周炎病变中表达FOXP3的细胞的表型。通过免疫磁珠从三名晚期牙周炎患者中建立CD4(+) FOXP3(+)牙龈T细胞克隆。分别通过逆转录聚合酶链反应和流式细胞术进行基因表达和表型分析。通过[³H]胸腺嘧啶核苷掺入法检测CD4(+) FOXP3(+) T细胞克隆对CD4(+) CD25(-) T细胞增殖反应的影响。
通过免疫组织化学发现，FOXP3表达于一些CD4(+) T细胞和CD25(+)细胞中，但在CD8(+) T细胞中未发现。尽管CD25基因有大量表达，但CD4(+) FOXP3(+)牙龈T细胞克隆上膜CD25的表达水平较低。虽然外周血CD4(+) CD25(+) FOXP3(+)细胞抑制CD4(+) CD25(-) T细胞的增殖，但CD4(+) CD25(低) FOXP3(+)牙龈T细胞克隆却显著增强其增殖。
我们的研究表明，牙周炎病变中大多数（如果不是全部）FOXP3(+) T细胞可被视为效应T细胞。牙龈T细胞克隆的效应活性可能归因于膜CD25表达水平较低。显然需要进一步研究以阐明这些T细胞在牙周疾病发病机制中的作用及其独特特征。
