Anti-B7-1 blocks mononuclear cell adherence in vasa recta after ischemia

Background. Blocking the costimulatory pathway by CTLA-4 Ig, reactive with both B7-1 and B7-2 costimulatory molecules, protects the kidney during acut e ischemia/reperfusion injury. This study investigated whether and how B7-1 and/or B7-2 proteins are involved in renal ischemia/reperfusion injury (IR I). Methods. Uninephrectomized rats were submitted to warm renal ischemia (30 m in) and received control monoclonal antibody (mAb: 17E3), anti-B7-1 (3H5). anti-B7-2 (24F), a combination of anti-B7-1/B7-2, or CTLA-4 Ig. Renal funct ion, morphology, and the kinetics of inflammatory cells were studied for a ten-day period, Binding sites of the injected antibodies were detected by s econdary staining with anti-mouse Ab. Results. Compared with controls, acute renal failure (ARF) in the anti-B7-1 group was attenuated both functionally and morphologically. Anti-B7-1/B7-2 and CTLA-4 Ig also were protective in IRI. ARF was not altered by anti-B7- 2 treatment. Two hours after reperfusion, B7-1 was expressed along the endo thelial cells of the ascending vasa recta. Expression of B7-1 increased ove r time during the first 24 hours and decreased thereafter. Two hours after reperfusion, adherence/accumulation of T cells and monocytes/macrophages wa s found in the vasa recta of the ischemic kidney. Anti-B7-1-treated animals had fewer T cells and monocytes/macrophages in the vasa recta compared wit h controls. Leukocyte accumulation in these vessels after anti-B7-2 treatme nt was not different from IRI controls, Conclusion. These observations strongly support the key role of the B7-1 pr otein in the protection of renal IRI through inhibition of T cell and monoc yte adherence at the level of the ascending vasa recta.