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.
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: Christopher S Nabel; Mariano Severgnini; Yin P Hung; Amy Cunningham-Bussel; Evisa Gjini; Katja Kleinsteuber; Lake J Seymour; Martha K Holland; Rachel Cunningham; Kristin D Felt; Marina Vivero; Scott J Rodig; Elena M Massarotti; Osama E Rahma; Lauren C Harshman Journal: Oncologist Date: 2019-05-14
Authors: Rebeca Hid Cadena; Wayel H Abdulahad; G A P Hospers; T T Wind; Annemieke M H Boots; Peter Heeringa; Elisabeth Brouwer Journal: Front Immunol Date: 2018-02-22 Impact factor: 7.561
Authors: B Wilde; A Mertens; S J Arends; R P Rouhl; R Bijleveld; J Huitema; S A Timmermans; J Damoiseaux; O Witzke; A M Duijvestijn; P van Paassen; R J van Oostenbrugge; J W Cohen Tervaert Journal: Arthritis Res Ther Date: 2016-06-23 Impact factor: 5.156