Cutting edge: CD4+CD25+ alloantigen-specific immunoregulatory cells that can prevent CD8+ T cell-mediated graft rejection: implications for anti-CD154 immunotherapy.
Blockade of CD40-CD154 interactions can facilitate long-term allograft acceptance in selected rodent and in primate models, but, due to the ability of CD154-independent CD8(+) T cells to initiate graft rejection, this strategy is not always effective. In this work we demonstrate that blockade of the CD40-CD154 pathway at the time of transplantation enables the generation of donor alloantigen-specific CD4(+)CD25(+) regulatory T cells, and that if the regulatory cells are present in sufficient numbers they can suppress allograft rejection mediated by CD154-independent CD8(+) T cells.
van Maurik
Andre van
Av
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.
Herber
Manuela
M
Wood
Kathryn J
KJ
Jones
Nick D
ND
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016038:Skin Transplantation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D019013:CD40 Antigens; D018984:Epitopes, T-Lymphocyte; D015375:Receptors, Interleukin-2; D023201:CD40 Ligand