CD40 ligand-dependent T cell activation: requirement of B7-CD28 signaling through CD40.
The role of CD40 ligand (CD40L) in the primary activation of T cells is not clear. The cellular and humoral immune responses to adenoviral vectors in a murine model of liver-directed gene transfer were studied to define the mechanisms responsible for CD40L-dependent T cell priming. CD40L-deficient mice did not develop effective cytotoxic T cells to transduced hepatocytes, and T cell-dependent B cell responses were absent. Full reconstitution of cellular and humoral immunity was achieved in CD40L-deficient mice by administration of an activating antibody to CD40 that increased expression of B7.2 on spleen cells. Wild-type mice could be made nonresponsive to vector by administration of antibodies to B7. Thus, CD40L-dependent activation of T cells occurs through signaling of CD40 in the antigen-presenting cell to enhance requisite costimulatory pathways that include B7.
Yang
Y
Y
Institute for Human Gene Therapy, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.
Wilson
J M
JM
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019076:Transgenes
D015703:Antigens, CD; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D023201:CD40 Ligand