Characterization of CD4+CD25+ natural regulatory T cells in the inflammatory infiltrate of human chronic periodontitis.
Periodontitis is an infectious disease, where putative periodontopathogens trigger chronic inflammatory and immune responses against periodontal structures, in which an unbalanced host response is also determinant to the disease outcome. It is reasonable to assume that patient susceptibility to periodontal tissue destruction could be determined by the balance between the response against periodontopathogens and regulatory mechanisms of these events mediated by suppressive T cells. In the present study, we identified and characterized natural regulatory T cells (Tregs) in the inflammatory infiltrate of human chronic periodontitis (CP) with emphasis on phenotypic analyses that were carried out to address the participation of Tregs in CP. Results showed that patients with CP presented increased frequency of T lymphocytes and CD4+CD25+ T cells in the inflammatory infiltrate of gingival tissues. These cells exhibited the phenotypic markers of Tregs such as forkhead box p3 (Foxp3), CTLA-4, glucocorticoid-inducible TNFR, CD103, and CD45RO and seemed to be attracted to the inflammation site by the chemokines CCL17 and CCL22, as their expression and its receptor CCR4 were increased in CP patients. Moreover, besides the increased detection of Foxp3 mRNA, diseased tissues presented high expression of the regulatory cytokines IL-10 and TGF-beta. In addition, the inflammatory infiltrate in CP biopsies was composed of CD25+Foxp3+ and CD25+TGF-beta+ cells, thus corroborating the hypothesis of the involvement of Tregs in the pathogenesis of CP. Finally, these results indicate that Tregs are found in the chronic lesions and must be involved in the modulation of local immune response in CP patients.
Cardoso
Cristina Ribeiro
CR
Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, Brazil.
Garlet
Gustavo Pompermaier
GP
Moreira
Ana Paula
AP
Júnior
Wálter Martins
WM
Rossi
Marcos Antônio
MA
Silva
João Santana
JS
D000328:Adult; D015704:CD4 Antigens / Q000276:immunology*; D002465:Cell Movement; D054414:Chemokine CCL17 / Q000378:metabolism; D054422:Chemokine CCL22 / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005881:Gingiva / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D018613:Microscopy, Confocal; D010518:Periodontitis / Q000276:immunology* / Q000473:pathology*; D010641:Phenotype; D019707:Receptors, Chemokine / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C106230:CCL17 protein, human; C515482:CCL22 protein, human; D015704:CD4 Antigens; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D019707:Receptors, Chemokine