Transfer of lymphocytes from mice with renal ischemia can induce albuminuria in naive mice: a possible mechanism linking early injury and progressive renal disease?
Severe ischemia-reperfusion injury (IRI) predisposes to long-term impairment in kidney function both in patients and experimentally through unknown mechanisms. Given emerging evidence implicating lymphocytes in the pathogenesis of early injury to kidney, liver, and lung after IRI, we hypothesized that kidney IRI would potentially release or expose normally sequestered antigens that would lead to proliferation of antigen-recognizing lymphocytes. This, in turn, would directly participate in progressive kidney injury. To test this hypothesis, we purified splenic lymphocytes from C57BL/6 mice with severe renal IRI or sham operation 6 wk postischemia and transferred these cells to normal mice. Donor mice with IRI had significant fibrosis and cellular inflammation. The recipient mice were followed for 6 or 12 wk. Donor lymphocytes were found to traffic into recipient kidney. Twelve weeks after transfer, kidneys from mice which received IRI-primed lymphocytes exhibited significantly increased urinary albumin excretion compared with lymphocytes from sham mice. Splenic CD3(+), CD4(+), CD3(+)CD25(+), and CD4(+)CD44(+) counts were significantly increased in mice after lymphocyte transfer from IRI mice vs. mice with lymphocytes from sham mice. These data demonstrate that lymphocytes from IRI mice can traffic to recipient kidney and directly mediate albuminuria. These data identify a novel mechanism by which initial kidney injury predisposes to long-term dysfunction and identify lymphocytes as potential therapeutic targets for progressive renal diseases.
Burne-Taney
Melissa J
MJ
Division of Nephrology, Johns Hopkins Univ. School of Medicine, Ross 965, 720 Rutland Ave, Baltimore, MD 21205, USA.
Liu
Manchang
M
Ascon
Dolores
D
Molls
Roshni R
RR
Racusen
Lorraine
L
Rabb
Hamid
H
D019264:Adoptive Transfer; D000419:Albuminuria / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005355:Fibrosis; D007156:Immunologic Memory; D007511:Ischemia / Q000276:immunology* / Q000473:pathology; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D009395:Nephritis, Interstitial / Q000276:immunology / Q000473:pathology; D051436:Renal Insufficiency, Chronic / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology