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


CONCLUSIONS
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.
Okui
T
T
Laboratory of Periodontology and Immunology, Department of Oral Health and Welfare, Niigata University Faculty of Dentistry, Niigata, Japan.
Ito
H
H
Honda
T
T
Amanuma
R
R
Yoshie
H
H
Yamazaki
K
K
D015704:CD4 Antigens / Q000032:analysis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002999:Clone Cells; D018920:Coculture Techniques; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis* / Q000235:genetics; D005786:Gene Expression Regulation; D005881:Gingiva / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis / Q000235:genetics; D010518:Periodontitis / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit