Impaired T cell-mediated macrophage activation in CD40 ligand-deficient mice
Stout, R.D.; Suttles, J.; Xu, J.; Grewal, I.S.; Flavell, R.A.
Journal of Immunology 156(1): 8-11
1996
ISSN/ISBN: 0022-1767 PMID: 8598498 Document Number: 457054
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.