Vδ2 T cell deficiency in granulomatosis with polyangiitis (Wegener's granulomatosis)

•Absolute numbers of γδ T cells are strongly reduced in the blood of GPA patients.•Only the Vδ2 subset of γδ T cells is depleted.•The remaining Vδ2 T cells still respond to microbial ligands.•Chronic exposure to microbes (S. aureus) might deplete Vδ2 T cells in GPA patients.

Previous studies have characterized phenotypic and functional alterations within T-cell receptor αβ-expressing T cells in patients with granulomatosis with polyangiitis (GPA). We analyzed the frequency, subset composition and in vitro activation of blood γδ T cells in GPA patients. We observed a significant reduction of γδ T cell numbers, due to the selective depletion of the Vδ2 subset which remained consistent over time upon repeated analysis. The loss of Vδ2 T cells was not due to migration into the inflamed lesions as very few γδ T cells were detected in inflammatory infiltrates. The memory subset distribution did not differ among Vδ2 T cells from healthy donors and GPA patients. Importantly, the remaining Vδ2 T cells were capable of responding to phosphoantigen stimulation in vitro. The marked depletion of blood Vδ2 T cells in GPA suggests cellular exhaustion, possibly due to chronic exposure to and continuous overstimulation by microbial phosphoantigens.