Characterization of CD4+ FOXP3+ T-cell clones established from chronic inflammatory lesions.

INTRODUCTION

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.