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

• Published in: Journal of Immunology 2006-09, Vol.177 (5), p.3380-3387
• Main Authors: Ascon, Dolores B, Lopez-Briones, Sergio, Liu, Manchang, Ascon, Miguel, Savransky, Vladimir, Colvin, Robert B, Soloski, Mark J, Rabb, Hamid
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - metabolism; Antigens, Differentiation, T-Lymphocyte - metabolism; CD3 Complex - immunology; CD3 Complex - metabolism; CD4 Antigens - immunology; CD4 Antigens - metabolism; Cell Movement; Immunohistochemistry; Interferon-gamma - biosynthesis; Kidney - immunology; Kidney - injuries; Kidney - pathology; Killer Cells, Natural - immunology; Lectins, C-Type; Lymphocyte Activation; Lymphocytes - cytology; Lymphocytes - immunology; Lymphocytes - metabolism; Male; Mice; Mice, Inbred C57BL; Phenotype; Reperfusion Injury - immunology; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Time Factors; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.177.5.3380

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-alpha and IFN-gamma 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.