CD40-CD40 ligand-independent activation of CD8+ T cells can trigger allograft rejection.
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.
Jones
N D
ND
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. nicholas.jones@surgery.ox.ac.uk
Van Maurik
A
A
Hara
M
M
Spriewald
B M
BM
Witzke
O
O
Morris
P J
PJ
Wood
K J
KJ
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000378:metabolism / Q000502:physiology*; D023201:CD40 Ligand; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002455:Cell Division / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D007108:Immune Tolerance / Q000276:immunology; D007274:Injections, Intraperitoneal; D007519:Isoantigens / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008814:Mice, Inbred NZB; D008822:Mice, Transgenic; D013045:Species Specificity
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D007519:Isoantigens; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand