IMPAIRED T-CELL-MEDIATED MACROPHAGE ACTIVATION IN CD40 LIGAND-DEFICIENT MICE

The expression of the ligand for CD40 (CD40L) is critical for inductio n of T cell-dependent Ab responses. To examine how critical the expres sion of CD40L is for induction of cell-mediated immune responses, the ability of T cells from CD40L knockout mice to activate macrophage eff ector function was assessed. CD4(+) T cells from CD40L-knockout mice w ere 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 o f the T cell, could activate neither macrophage production of inflamma tory cytokines (TNF-alpha) nor generation of reactive nitrogen interme diates. 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 di splay a deficiency in T cell-dependent macrophage-mediated immune resp onses.