Transplant surgery injury recruits recipient MHC class II-positive leukocytes into the kidney

Background. CD4 T cells, which are stimulated by the "indirect pathway" of antigen-presentation, participate in rejection. These T cells are sensitize d by recipient major histocompatibility complex (MHC) class II-positive leu kocytes that migrate into the transplant. Therefore, an important early ste p in rejection is the immigration of these recipient MHC class II-positive leukocytes into the renal transplant. The regulation of this early step is not understood. We now test the hypothesis that such leukocytes immigrate i n to the renal transplant in response to ischemic injury occurring during t he transplant procedure. Methods. We transplanted Brown Norway (BN) kidneys into Fl Lewis/Brown Norw ay (L/BN) recipients. The Fl recipients are tolerant to the parental BN ant igens, and any infiltration of recipient MHC class II-positive leukocytes r esults from injury occurring during transplantation surgery. In addition, i schemia/reperfusion injury was also induced by temporarily occluding the na tive renal arteries for 30 minutes. Transplanted kidneys and native kidneys , which suffered ischemia/reperfusion injury, were studied by immunohistoch emistry on days 3, 7, 14, and 28 after surgery. Staining by the new monoclo nal antibody (mAb) OX62 and antibodies to MHC class II identified dendritic cells. In addition, the following monoclonal antibodies identified: gamma/ delta T cells, V65: B cells, OX33; cells that may be macrophages, dendritic cells, or dendritic cell precursors, ED1 (+) and OX62 (-); and recipient c lass II MHC, OX3. Results. After transplantation, the serum creatinine increased to 4 mg/dl a nd then decreased, which was consistent with reversible injury during trans plantation and the absence of rejection. We found that the injury of transp lantation itself resulted in the infiltration of recipient MHC class II-pos itive leukocytes into the transplanted kidney. This infiltrate peaked at da ys 7 to 14 after surgery. The inflammation was peritubular and patchy and i nvolved cortex and outer medulla. Double staining for OX62 and OX3 identifi ed some of the infiltrating leukocytes as dendritic cells. Other recipient leukocytes were MHC class II positive, ED1 positive, and OX62 negative. We also found that MHC class II leukocytes, including dendritic cells, infiltr ated native kidneys injured by ischemia/reperfusion injury. Conclusion. To our knowledge, this is the first demonstration that injury t o the kidney during transplantation recruits recipient MHC class II-positiv e leukocytes into the kidney. Some of these leukocytes are dendritic cells.