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

Jeffrey G. Penfield, Yuqin Wang, Shujun Li, Mariusz A. Kielar, Stanley C. Sicher, D. Rouan Jeyarajah, Christopher Y. Lu

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Background. CD4 T cells, which are stimulated by the 'indirect pathway' of antigen-presentation, participate in rejection. These T cells are sensitized by recipient major histocompatibility complex (MHC) class II- positive leukocytes that migrate into the transplant. Therefore, an important early step 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 into the renal transplant in response to ischemic injury occurring during the transplant procedure. Methods. We transplanted Brown Norway (BN) kidneys into F1 Lewis/Brown Norway (L/BN) recipients. The F1 recipients are tolerant to the parental BN antigens, and any infiltration of recipient MHC class II-positive leukocytes results from injury occurring during transplantation surgery. In addition, ischemia/reperfusion injury was also induced by temporarily occluding the native renal arteries for 30 minutes. Transplanted kidneys and native kidneys, which suffered ischemia/reperfusion injury, were studied by immunohistochemistry on days 3, 7, 14, and 28 after surgery. Staining by the new monoclonal 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 class II MHC, OX3. Results. After transplantation, the serum creatinine increased to 4 mg/dl and then decreased, which was consistent with reversible injury during transplantation and the absence of rejection. We found that the injury of transplantation itself resulted in the infiltration of recipient MHC class II-positive leukocytes into the transplanted kidney. This infiltrate peaked at days 7 to 14 after surgery. The inflammation was peritubular and patchy and involved cortex and outer medulla. Double staining for OX62 and OX3 identified 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, infiltrated native kidneys injured by ischemia/reperfusion injury. Conclusion. To our knowledge, this is the first demonstration that injury to the kidney during transplantation recruits recipient MHC class II-positive leukocytes into the kidney. Some of these leukocytes are dendritic cells.

Original languageEnglish (US)
Pages (from-to)1759-1769
Number of pages11
JournalKidney international
Volume56
Issue number5
DOIs
StatePublished - Jan 1 1999

Keywords

  • Acute renal failure
  • Dendritic cell
  • Ischemia
  • Major histocompatibility complex
  • Transplantation

ASJC Scopus subject areas

  • Nephrology

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