Altered intragraft immune responses and imroved renal function in MHC class II-deficient mouse kidney allografts

Roslyn B. Mannon, Carolyn Doyle, Robert Griffiths, Matilde Bustos, Jeffrey L. Platt, Thomas M. Coffman

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Background. During renal allograft rejection, expression of MHC class II antigens is up-regulated on the parenchymal cells of the kidney. This up- regulation of MHC class II proteins may stimulate the intragraft alloimmune response by promoting their recognition by recipient CD4+ T cells. In previous studies, absence of donor MHC class II antigens did not affect skin graft survival, but resulted in prolonged survival of cardiac allografts. Methods. To further explore the role of MHC class II antigens in kidney graft rejection, we performed vascularized kidney transplants using donor kidneys from A(β)b-deficient mice that lack MHC class II expression. Results. At 4 weeks after transplant, GFR was substantially depressed in control allografts (2.18±0.46 ml/min/kg) compared to nonrejecting isografts (7.98±1.62 ml/min/kg; P<0.01), but significantly higher in class II- allografts (4.38±0.60 ml/min/kg; P<0.05). Despite the improvement in renal function, class II- allograft demonstrated histologic features of acute rejection, not unlike control allografts. However, morphometric analysis at 1 week after transplantation demonstrated significantly fewer CD4+ T cells infiltrating class II- allografts (12.8±1.2 cells/mm2) compared to controls (25.5±2.6 cells/mm2; P=0.0007). Finally, the intragraft profile of cytokines was altered in class II- allografts, with significantly reduced expression of Th2 cytokine mRNA compared to controls. Conclusions. These results support a role of MHC class II antigens in the kidney regulating immune cells within the graft. Further, effector pathways triggered by class II antigens promote renal injury during rejection.

Original languageEnglish (US)
Pages (from-to)2137-2143
Number of pages7
JournalTransplantation
Volume69
Issue number10
DOIs
StatePublished - May 27 2000

ASJC Scopus subject areas

  • Transplantation

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