T‐cell receptor αβ⁺ double‐negative T cells in the kidney are predominantly extravascular and increase in abundance in response to ischemia–reperfusion injury

Abstract

T‐cell receptor+CD4−CD8− double‐negative (DN) T cells are a population of T cells present in low abundance in blood and lymphoid organs, but enriched in various organs including the kidney. Despite burgeoning interest in these cells, studies examining their abundance in the kidney have reported conflicting results. Here we developed a flow cytometry strategy to clearly segregate DN T cells from other immune cells in the mouse kidney and used it to characterize their phenotype and response in renal ischemia–reperfusion injury (IRI). These experiments revealed that in the healthy kidney, most DN T cells are located within the renal parenchyma and exhibit an effector memory phenotype. In response to IRI, the number of renal DN T cells is unaltered after 24 h, but significantly increased by 72 h. This increase is not related to alterations in proliferation or apoptosis. By contrast, adoptive transfer studies indicate that circulating DN T cells undergo preferential recruitment to the postischemic kidney. Furthermore, DN T cells show the capacity to upregulate CD8, both in vivo following adoptive transfer and in response to ex vivo activation. Together, these findings provide novel insights regarding the phenotype of DN T cells in the kidney, including their predominant extravascular location, and show that increases in their abundance in the kidney following IRI occur in part as a result of increased recruitment from the circulation. Furthermore, the observation that DN T cells can upregulate CD8 in vivo has important implications for detection and characterization of DN T cells in future studies.

GPX3 and GSTT1 as biomarkers related to oxidative stress during renal ischemia reperfusion injuries and their relationship with immune infiltration

“…Snelgrove et al. used T-cell-deficient mice and overexpression to metastasize T cells, finding that T cells played an important role in RIRIs ( 13 ). Kinsey et al.…”

“…In RIRIs, T-cellantigen-specific or nonspecific responses are thought to play a crucial role. Snelgrove et al used T-cell-deficient mice and overexpression to metastasize T cells, finding that T cells played an important role in RIRIs (13). Kinsey et al found that the local inflammatory response of kidneys was weakened due to CD4+ T cell supplementation in mouse RIRI models, which had a protective effect on RIRI damage (14).…”