Inhibitory Signals Mediated by Programmed Death-1 Are Involved With T-Cell Function in Chronic Periodontitis

Autor(es)

Figueira, Eduardo Aleixo ^[1] ; Rubo de Rezende, Maria Lucia ^[2] ; Torres, Sergio Aparecido ^[1] ; Garlet, Gustavo Pompermaier ^[1] ; Lara, Vanessa Soares ^[3] ; Santos, Carlos Ferreira ^[1] ; Avila-Campos, Mario Julio ^[4] ; da Silva, Joao Santana ^[5] ; Campanelli, Ana Paula ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Bauru Sch Dent, Dept Biol Sci, BR-17012901 Bauru, SP - Brazil

^[2] Univ Sao Paulo, Bauru Sch Dent, Div Periodontol, Dept Prosthodont, BR-17012901 Bauru, SP - Brazil

^[3] Univ Sao Paulo, Bauru Sch Dent, Div Oral Pathol, Dept Stomatol, BR-17012901 Bauru, SP - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049 Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Periodontology; v. 80, n. 11, p. 1833-1844, NOV 2009.
• Citações Web of Science: 7

Resumo

Background: Inhibitory signals mediated via molecules such as programmed death-1 (PD-1) play a critical role in downmodulating immune responses and maintaining peripheral tolerance. We investigated the involvement of cytokines and PD-1 engagement in mediating the T-cell unresponsiveness to bacterial and ubiquitous antigens in periodontal diseases. Methods: Gingival and peripheral blood samples from healthy individuals and patients with chronic periodontitis were collected and used for the subsequent assays. Leukocytes in the lesion site and blood were evaluated using flow cytometry. The production of interferon-gamma, interleukin-10, and transforming growth factor-P proteins was evaluated by enzyme-linked immunosorbent assay (ELISA), and the presence of PD-1+cells in the inflamed gingiva was confirmed by immunofluorescence confocal microscopy for CD4 and PD-1 colocalization. Results: T cells from patients with chronic periodontitis proliferated poorly in response to Aggregatibacter actinomycetem comitans (previously Actinobacillus actinomycetemcomitans) antigen. T-cell unresponsiveness was not associated with imbalanced cytokine production. However, T cells from patients with chronic periodontitis expressed significantly higher levels of PD-1 either upon isolation or after culture with antigens. Moreover, PD-1 blocking did not result in significant T-cell proliferation in cells cultured with phytohemagglutinin or bacterial antigens. The blockade of PD-1 resulted in the increased production of IFN-gamma. In addition, CD4+ and CD8+ T cells expressing PD-1 accumulated in lesions with chronic periodontitis. Conclusion: These data show that PD-1 engagement could be involved in the modulation of IFN-gamma production by T cells in patients with chronic periodontitis. J Periodontol 2009,80:1833-1844. (AU)

• Processo FAPESP: 04/06704-0 - Envolvimento de sinais co-estimulatorios na progressao da doenca periodontal humana.
• Beneficiário: Ana Paula Campanelli
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 05/53391-0 - Envolvimento de sinais co-estimulatorios na progressao da doenca periodontal humana.
• Beneficiário: Eduardo Aleixo Figueira
• Modalidade de apoio: Bolsas no Brasil - Mestrado