Impaired T cell-mediated macrophage activation in CD40 ligand-deficient mice.
The expression of the ligand for CD40 (CD40L) is critical for induction of T cell-dependent Ab responses. To examine how critical the expression of CD40L is for induction of cell-mediated immune responses, the ability of T cells from CD40L knockout mice to activate macrophage effector function was assessed. CD4+ T cells from CD40L-knockout mice were fourfold less effective than +/+ T cells in activating the nitric oxide response in allogeneic macrophages. CD40L-knockout T cells that were fixed with paraformaldehyde after a 6-h activation period, a time point at which CD40L dominates the macrophage-activating capability of the T cell, could activate neither macrophage production of inflammatory cytokines (TNF-alpha) nor generation of reactive nitrogen intermediates. After 24 h of activation, however, both CD40L-knockout and +/+ T cells could induce similar but weak responses from the macrophages. This study demonstrates that animals deficient in CD40L expression display a deficiency in T cell-dependent macrophage-mediated immune responses.
Stout
R D
RD
Department of Microbiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614-0579, USA.
Suttles
J
J
Xu
J
J
Grewal
I S
IS
Flavell
R A
RA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000235:genetics*; D023201:CD40 Ligand; D002478:Cells, Cultured; D008024:Ligands; D008262:Macrophage Activation / Q000235:genetics*; D008264:Macrophages / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency*; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008822:Mice, Transgenic
D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand