The effect of murine anti-thymocyte globulin on experimental kidney warm ischemia-reperfusion injury in mice.
Kidney ischemia-reperfusion injury (IRI) is an important contributor to delayed graft function (DGF) and poor outcome of allografts. Small clinical studies suggest a beneficial role for human anti-thymocyte globulin (ATG) in DGF. We investigated the short-term effect of mouse anti-thymocyte globulin (mATG) on kidney warm IRI in mice. We administered either mATG, rabbit immunoglobulin (RIgG), or saline with different dosing schedules in three different IRI models: 30 min bilateral, 60 min bilateral, and 45min unilateral IRI. mATG effectively depleted circulating T cells but had less effect on kidney-infiltrating T cells. There was no difference in serum creatinine levels between groups in each study. Scoring of renal tubular damage and regenerating tubules revealed no difference between groups. The percentage of CD3(+)CD4(-)CD8(-) double-negative (DN) T cells, which were reported to contribute to the pathogenesis of lupus nephritis, increased and the percentages of regulatory T cells and NK cells decreased in the post-ischemic kidneys of mATG treated mice. mATG did not alter the expression of pro-inflammatory cytokines such as IFN-gamma or anti-inflammatory cytokines such as IL-10 in post-ischemic kidneys. mATG treatment, whether initiated before ischemia or immediately after reperfusion, had minimal effects on renal injury following warm IRI in mice.
Jang
Hye Ryoun
HR
Nephrology Division, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. shinehr@gmail.com
Gandolfo
Maria Teresa
MT
Ko
Gang Jee
GJ
Racusen
Lorraine
L
Rabb
Hamid
H
D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001772:Blood Cell Count; D018925:Chemokines / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D007074:Immunoglobulin G / Q000627:therapeutic use; D007668:Kidney / Q000098:blood supply / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007672:Kidney Cortex / Q000473:pathology; D007679:Kidney Medulla / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011817:Rabbits; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D013154:Spleen / Q000473:pathology; D015996:Survival Rate; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D000961:Antilymphocyte Serum; D018925:Chemokines; D016207:Cytokines; D007074:Immunoglobulin G; D003404:Creatinine