Phenotypic and Functional Characterization of Kidney-Infiltrating Lymphocytes in Renal Ischemia Reperfusion Injury

Abstract

T and B lymphocytes have been implicated in the pathogenesis of renal ischemia reperfusion injury (IRI). The trafficking of lymphocytes into kidneys during IRI has been postulated to underlie this effect, but has not been rigorously studied. We therefore characterized the lymphocyte populations infiltrating into mouse kidneys 3 and 24 h after renal IRI. Immunohistochemistry and flow cytometry staining of kidney lymphocytes showed increased trafficking of CD3+ T cells and CD19+ B cells in both sham-operated and IRI mice 3 h after renal IRI. In the IRI mice, increased infiltration of NK1.1+ and CD4+NK1.1+ cells compared with normal and sham-operated mice was observed 3 and 24 h after renal IRI, respectively. After 24 h of renal IRI, the decreased percentages of CD3+, CD19+, and NK1.1+ populations in the IRI mice compared with control groups were observed. Increased TNF-α and IFN-γ production of kidney infiltration CD3+ T cells in IRI mice but not sham-operated mice was found. Unexpectedly, isolation and transfer of kidney-infiltrating lymphocytes 24 h after renal IRI into T cell-deficient mice reduced their functional and histological injury after renal IRI, suggesting that kidney-infiltrating lymphocytes could have a protective function. These quantitative, qualitative, and functional changes in kidney lymphocytes provide mechanistic insight into how lymphocytes modulate IRI, as well as demonstrating that abdominal surgery alone leads to lymphocyte changes in kidney.

Overexpression of cGMP-dependent protein kinase I (PKG-I) attenuates ischemia-reperfusion-induced kidney injury

“…The labeled cells were analyzed by flow cytometry. For detection of macrophages from the pool of kidney mononuclear cells, kidney mononuclear cells were isolated from kidneys using the method as described previously (1). Briefly, the cell pellet was suspended in 36% Percoll (Sigma), slowly loaded onto 72% Percoll, and centrifuged at 1,000 g for 30 min at room temperature.…”

Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study

“…7,30 Finally, WBCs are involved in the kidney's response to injury as evidenced by leukocyte infiltration in kidney tissues of patients with CKD and in experimental models. [31][32][33] Lower mtDNA copy number might alter the role of WBCs and platelets in injury response. The inclusion of mtDNA copy number derived from WBCs and platelets in experiments investigating the role of mitochondrial dysfunction in CKD can increase our understanding on the potential role of these cells in the pathogenesis of CKD and may lead to novel insight for the prevention or treatment of CKD.…”

Sulfatide-Reactive Natural Killer T Cells Abrogate Ischemia-Reperfusion Injury

“…9 -11 However, only a few reports have investigated the role of NKT cells in kidney IRI, despite the fact that these cells are known to traffic into postischemic kidneys as early as 3 hours after IRI. 12,13 NKT cells have been proposed as a bridge between the innate and adaptive immune systems. 14 -16 NKT cell recruitment into the site of injury was directed by the interaction between CXCL16 and CXCR6, which is expressed on NKT cells and activated Th1 cells.…”