CD4(+) T cells tolerized ex vivo to host alloantigen by anti-CD40 ligand (CD40L:CD154) antibody lose their graft-versus-host disease lethality capacity but retain nominal antigen responses.
A major goal of the transplant field is to tolerize donor T cells to prevent graft-versus-host disease (GVHD) (1). We describe an ex vivo approach in which the blockade of CD40 ligand (CD40L:CD154):CD40 interactions, a pathway required for optimal T cell expansion, induces donor CD4(+) T cells to become tolerant to host alloantigens (2). High doses of tolerized cells did not cause GVHD lethality in vivo. T cells had intact responses to antigens not present during tolerization. Tolerance was long lived and not readily reversible in vivo. These data have significant implications for the use of tolerization approaches to prevent human GVHD.
Department of Pediatrics, Division of Bone Marrow Transplantation, University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, USA. blaza001@maroon.tc.umn.edu
B R
BR
Blazar
P A
PA
Taylor
R J
RJ
Noelle
D A
DA
Vallera
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D002478:Cells, Cultured; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D013047:Specific Pathogen-Free Organisms
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D007376:Interleukin-2; D007519:Isoantigens; D008562:Membrane Glycoproteins; D023201:CD40 Ligand