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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.

Type

Journal article

Journal

J Immunol

Publication Date

15/07/2000

Volume

165

Pages

1111 - 1118

Keywords

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