Aberrant expression of the negative costimulator PD-1 on T cells in granulomatosis with polyangiitis

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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.

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