title: Aberrant expression of the negative costimulator PD-1 on T cells in granulomatosis with polyangiitis.
abstract: OBJECTIVE
  Persistent T-cell activation is frequently observed in granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis). T-cell activation is usually balanced by negative costimulatory molecules. The negative costimulator programmed death receptor-1 (PD-1) and its relevance to T-cell immunity have not been studied so far in GPA. Thus it is the aim of the study to characterize the role of PD-1 in GPA.
  
  
  METHODS
  Thirty-two patients suffering from GPA and 19 age-matched healthy controls (HCs) were enrolled. T-lymphocyte subsets from peripheral blood were analysed by flow cytometry for the expression of PD-1. The frequency of memory T cells and T cells producing pro-inflammatory cytokines was determined. Renal biopsies from GPA patients were stained for CD3 and PD-1.
  
  
  RESULTS
  PD-1 expression was increased on T-helper cells (Th cells) from GPA patients as compared with HCs. In addition, parameters of persistent T-cell activation and production of pro-inflammatory cytokines were positively associated with numbers of PD-1(+) Th cells in patients but not in HCs. Latent infection with CMV seemed to enhance PD-1 expression on CD4(+) and CD4(+)CD25(-) T cells. Interestingly, expression of PD-1 on CD4(+)CD25(+)T cells was inversely correlated with relapse rate. Importantly, lesional T cells were mostly lacking PD-1.
  
  
  CONCLUSIONS
  The expression of the negative costimulator PD-1 is altered in GPA and might counterbalance persistent T-cell activation.
authors.affiliation: Department of Nephrology, University Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wilde
authors.forename: Fan
authors.initials: F
authors.lastname: Hua
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dolff
authors.forename: Cao
authors.initials: C
authors.lastname: Jun
authors.forename: Xin
authors.initials: X
authors.lastname: Cai
authors.forename: Christof
authors.initials: C
authors.lastname: Specker
authors.forename: Thorsten
authors.initials: T
authors.lastname: Feldkamp
authors.forename: Andreas
authors.initials: A
authors.lastname: Kribben
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Cohen Tervaert
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
mesh_terms: D001706:Biopsy; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D014890:Granulomatosis with Polyangiitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D007424:Intracellular Fluid / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor