Aim: To characterise γ/δ T cells present in human fibrotic chronic kidney disease (CKD).
Background: γ/δ T cells are effector lymphocytes with important functional roles in chronic inflammatory processes. Mouse studies attribute a pathological role for γ/δ T cells in immune-mediated models of kidney disease. This study evaluates, for the first time, γ/δ T cells in human kidney disease.
Methods: We extracted γ/δ T cells from healthy kidney tissue and diseased biopsies with and without fibrosis. γ/δ T cells were identified, enumerated and phenotyped by twelve-colour flow cytometry. Localisation and production of the pro-inflammatory cytokine IL-17 by γ/δ T cells was examined by multi-colour immunofluorescent microscopy.
Results: We detected significantly elevated numbers of γ/δ T cells (CD45+CD3+γ/δ+) in diseased biopsies with interstitial fibrosis compared with diseased biopsies without fibrosis and healthy kidney tissue. The increased numbers of γ/δ T cells correlated significantly with loss of kidney function (eGFR). Furthermore, expression levels of CD161, a marker of human IL-17-producing T cells, were increased on γ/δ T cells from fibrotic biopsies compared with non-fibrotic kidney tissue. Immunofluorescent analysis of fibrotic kidney tissue localised the accumulation of γ/δ T cells within the tubulointerstitial compartment, adjacent to proximal tubular epithelial cells, defined as tubular cells expressing aquaporin-1. Notably, we identified these tubulointerstitial γ/δ T cells as a source of pro-inflammatory cytokine IL-17.
Conclusion: The correlation of IL-17-producing γ/δ T cells with histologically and functionally more severe CKD suggests a pathological role. Further functional dissection of kidney γ/δ T cells is now required for precision targeting of therapeutics to key checkpoint molecules to disrupt their role in CKD.