Renal double negative T cells: unconventional cells in search of a function

Renal double negative T cells: increasing importance in health and disease

“…A main reason is the lack of surface markers that specifically identify DN T cells, which is necessary to replace current approaches that use exclusion to identify DN T cells. We agree with their point that the best current markers to identify DNT cells is a combination of expression and absence of select surface molecules leading to the profile of CD45+TCRαβ+CD1d-CD4-CD8- (2). As stated in their commentary, discrepancies in DN T cell frequency in different publications may be due to different gating strategies and different methods of tissue processing.…”

The Tryptophan Metabolizing Enzyme Indoleamine 2,3-Dioxygenase 1 Regulates Polycystic Kidney Disease Progression

“…Given our previously published findings that CD8 + T cells play an anti-cystogenic role in the Pkd1 RC/RC model, this increase in CD8 + T cell numbers supports a reduction in cyst severity in PKD Ido1 -/- animals compared to control(43). This increase of CD8 + T cells is counterbalanced by a decrease in double negative T cells, whose functional role has not been studied in PKD, but we and others have reported that their numbers increase in ADPKD compared to control in Pkd1 RC/RC kidneys as well as ADPKD patient kidneys ( Supplemental Figure 3D )(50, 58).…”

“…We compared kidney immune cell types of Pkd1 RC/RC ; Ido1 +/+ and Pkd1 RC/RC ; Ido1 -/- mice at 3mo and 6mo of age using flow cytometry of kidney single cell suspensions ( Figure 3, Supplemental Figure 3 )(41, 43, 50). Overall, we found that the observed decreased PKD severity in Pkd1 RC/RC ; Ido1 -/- mice compared to Pkd1 RC/RC Ido1 +/+ mice at 6mo of age was associated with lower numbers of kidney immune cells (CD45 + , Figure 3A ) and a significant decrease in infiltrating (F4/80 lo ; CD11b + ) and resident (F4/80 hi ; CD11b + ) macrophages, neutrophils (GR1 + ), dendritic cells (DCs, CD11b + ; CD11c + ) and natural killer cells (NK cells, NKp46 + ) compared to control ( Figure 3B, Supplemental Figure 3A-C ).…”

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

“…A more stringent flow cytometric protocol identifies a bona fide double-negative T-cell population Identifying renal TCRab + DN T cells via flow cytometry solely on the basis of their lack of specific surface markers has the potential to contribute to inconsistency in findings. Here we addressed this issue using a flow cytometry gating strategy that makes use of a dump channel to exclude many of the other immune cells present in healthy kidneys, particularly renal mononuclear phagocytes that are CD4 À CD8 À but may be TCRb + , 19,25,26 and B cells (Figure 1a). Renal leukocytes in digested kidneys were identified based on forward scatter/ side scatter profiles and dead cells excluded by a live/dead stain, prior to gating on CD45 to identify intrarenal leukocytes.…”