CD40-CD40 ligand-independent activation of CD8+ T cells can trigger allograft rejection

N D Jones, A Van Maurik, M Hara, B M Spriewald, O Witzke, P J Morris, K J Wood

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In experimental transplantation, blockade of CD40-CD40 ligand (CD40L) interactions has proved effective at permitting long-term graft survival and has recently been approved for clinical evaluation. We show that CD4+ T cell-mediated rejection is prevented by anti-CD40L mAb therapy but that CD8+ T cells remain fully functional. Furthermore, blocking CD40L interactions has no effect on CD8+ T cell activation, proliferation, differentiation, homing to the target allograft, or cytokine production. We conclude that CD40L is not an important costimulatory molecule for CD8+ T cell activation and that following transplantation donor APC can activate recipient CD8+ T cells directly without first being primed by CD4+ T cells.
Original languageEnglish
Pages (from-to)1111-8
Number of pages8
JournalJournal of Immunology
Issue number2
Publication statusPublished - 15 Jul 2000


  • Cell Movement
  • Injections, Intraperitoneal
  • Animals
  • Antigens, CD40
  • Membrane Glycoproteins
  • Heart Transplantation
  • Mice
  • Mice, Transgenic
  • Immune Tolerance
  • CD4-Positive T-Lymphocytes
  • CD40 Ligand
  • Lymphocyte Activation
  • Antibodies, Monoclonal
  • Mice, Inbred CBA
  • Isoantigens
  • Mice, Inbred NZB
  • Graft Rejection
  • Antibodies, Blocking
  • CD8-Positive T-Lymphocytes
  • Mice, Inbred C57BL
  • Species Specificity
  • Ligands
  • Cell Division


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