title: Inhibitory signals mediated by programmed death-1 are involved with T-cell function in chronic periodontitis.
abstract: 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-beta 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-gamma. In addition, CD4+ and CD8+ T cells expressing PD-1 accumulated in lesions with chronic periodontitis.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors.forename: Eduardo Aleixo
authors.initials: EA
authors.lastname: Figueira
authors.forename: Maria Lúcia Rubo
authors.initials: ML
authors.lastname: de Rezende
authors.forename: Sergio Aparecido
authors.initials: SA
authors.lastname: Torres
authors.forename: Gustavo Pompermaier
authors.initials: GP
authors.lastname: Garlet
authors.forename: Vanessa Soares
authors.initials: VS
authors.lastname: Lara
authors.forename: Carlos Ferreira
authors.initials: CF
authors.lastname: Santos
authors.forename: Mario Julio
authors.initials: MJ
authors.lastname: Avila-Campos
authors.forename: João Santana
authors.initials: JS
authors.lastname: da Silva
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Campanelli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology; D016301:Alveolar Bone Loss / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000032:analysis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D055113:Chronic Periodontitis / Q000097:blood / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D005881:Gingiva / Q000473:pathology; D005891:Gingivitis / Q000097:blood / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D016753:Interleukin-10 / Q000032:analysis / Q000276:immunology; D007962:Leukocytes / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D017622:Periodontal Attachment Loss / Q000276:immunology; D010514:Periodontal Pocket / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma