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Published online before print May 1, 2008

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(Journal of Leukocyte Biology. 2008;84:311-318.)
© 2008 by Society for Leukocyte Biology

Characterization of CD4⁺CD25⁺ natural regulatory T cells in the inflammatory infiltrate of human chronic periodontitis

Cristina Ribeiro Cardoso^*,1, Gustavo Pompermaier Garlet^,1, Ana Paula Moreira^*, Wálter Martins Júnior, Marcos Antônio Rossi and João Santana Silva^*,2

Departments of
^* Biochemistry and Immunology and
Pathology, School of Medicine of Ribeirão Preto, and
Department of Biological Sciences, School of Dentistry of Bauru, University of São Paulo, São Paulo, Brazil; and
Department of Periodontics, Dentistry School, University of Ribeirão Preto, Ribeirão Preto, Brazil

²Correspondence: School of Medicine of Ribeirão Preto, USP, Department of Biochemistry and Immunology, Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil. E-mail: jsdsilva{at}fmrp.usp.br

ABSTRACT

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-β. In addition, the inflammatory infiltrate in CP biopsies was composed of CD25⁺Foxp3⁺ and CD25⁺TGF-β⁺ 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.

Key Words: periodontal disease • Tregs • gingival biopsies • immune regulation • inflammation