title: Increased programmed death-1 expression on CD4+ T cells in cutaneous T-cell lymphoma: implications for immune suppression.
abstract: OBJECTIVE
  To investigate the expression profile of programmed death-1 (PD-1) on T cells derived from patients with cutaneous T-cell lymphoma (CTCL), analyze a potential mechanism responsible for upregulation of PD-1, and assess the correlation between blockade of its signaling pathway and improvement in immunological function.
  
  
  METHODS
  Translation research study.
  
  
  METHODS
  University medical center.
  
  
  METHODS
  Patients with Sézary syndrome, patients with mycosis fungoides, and healthy volunteers.
  
  
  METHODS
  Programmed death-1 expression on T cells by flow cytometry and interferon γ (IFN-γ) production by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  We report significantly increased PD-1 expression on CD4(+) T cells from patients with Sézary syndrome compared with CD4(+) T cells from patients with mycosis fungoides and healthy volunteers. Both CD26(-) and CD26(+) populations of CD4(+) T cells demonstrated increased expression of PD-1, which was upregulated by the engagement of the T-cell receptor with anti-CD3/CD28 antibodies. In addition, blockade of the signaling pathway with blocking antibodies to PD-1 or its ligand PD-L1 led to an increase in the capacity to produce IFN-γ among some patients. Finally, longitudinal studies of 1 patient revealed a progressive decrease in PD-1 expression on CD4(+) T cells with improvement of clinical disease.
  
  
  CONCLUSIONS
  Our data imply that increased PD-1 expression in Sézary syndrome may play a role in attenuating the immune response and provide further insight into the immunosuppressive nature of CD4(+) T cells in Sézary syndrome and suggest another potential means of targeted therapy for these patients.
authors: Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. samimi@mail.med.upenn.edu
authors: Sara
authors: S
authors: Samimi
authors: Bernice
authors: B
authors: Benoit
authors: Katherine
authors: K
authors: Evans
authors: E John
authors: EJ
authors: Wherry
authors: Louise
authors: L
authors: Showe
authors: Maria
authors: M
authors: Wysocka
authors: Alain H
authors: AH
authors: Rook
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy; D009363:Neoplasm Proteins; D061026:Programmed Cell Death 1 Receptor; D012751:Sezary Syndrome / Q000097:blood* / Q000276:immunology / Q000473:pathology; D012878:Skin Neoplasms / Q000097:blood* / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D009363:Neoplasm Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor