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Inhibitory Signals Mediated by Programmed Death‐1 Are Involved With T‐Cell Function in Chronic Periodontitis
Author(s) -
Figueira Eduardo Aleixo,
de Rezende Maria Lúcia Rubo,
Torres Sergio Aparecido,
Garlet Gustavo Pompermaier,
Lara Vanessa Soares,
Santos Carlos Ferreira,
AvilaCampos Mario Julio,
da Silva João Santana,
Campanelli Ana Paula
Publication year - 2009
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.2009.090057
Subject(s) - aggregatibacter actinomycetemcomitans , chronic periodontitis , periodontitis , antigen , immune system , t cell , cd8 , immunology , flow cytometry , cytokine , medicine , biology , porphyromonas gingivalis
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‐γ, interleukin‐10, and transforming growth factor‐β 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 actinomycetemcomitans (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‐γ. 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‐γ production by T cells in patients with chronic periodontitis.