Thymic recognition of class II major histocompatibility complex allopeptides induces donor-specific unresponsiveness to renal allografts

Mohamed H. Sayegh, Norberto Perico, Ornella Imberti, Wayne W. Hancock, Charles B. Carpenter, Giuseppe Remuzzi

Research output: Contribution to journalArticle

Abstract

Recent data show that intrathymic injection of allogeneic cells induces donor-specific unresponsiveness to allografts. There is also evidence to suggest that, in addition to recognizing intact MHC molecules, T cells can recognize processed MHC peptides, although the role of this indirect mode of allorecognition in allograft rejection is unknown. We report that a single intrathymic injection of 100 μg of a mixture of eight 25-mer synthetic polymorphic class II MHC allopeptides, representing the full-length sequence of RT1.Buβ and RT1.Duβ (WF) into incompatible (RT11) LEW recipients, induced a state of long-term unresponsiveness to subsequent engraftment 2 days later of WF, but not third party (RT1n) BN renal allografts. Intrathymic injection of 100 μg of either RT1.Buβ or RT1.Duβ peptide mixtures alone were insufficient to prolong renal allograft survival. Intravenous or intrasplenic injection of the allopeptide mixture did not affect renal allograft survival, establishing the role of thymic recognition of class II MHC allopeptides in inducing systemic unresponsiveness. The induction of intrathymic donor-specific unresponsiveness was abrogated if thymectomy was performed on the day of renal transplantation or 5 days later. PBLs from long-term surviving animals exhibited marked reduction of proliferation to WF, but not third party BN stimulator lymphocytes in the standard mixed lymphocyte response assay in vitro. These observations emphasize the role of recognition of processed MHC molecules in vascularized allograft rejection and confirm the role of the thymus in acquired systemic tolerance to alloantigens.

Original languageEnglish
Pages (from-to)461-465
Number of pages5
JournalTransplantation
Volume56
Issue number2
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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