Impaired ability of MHC class II-/- dendritic cells to provide tumor protection is rescued by CD40 ligation

The contribution of CD4(+) T cells to dendritic cell (DC) activation and to the induction of CD8(+) T cell responses in vivo was investigated using a model of antitumor immune responses. Immunization with peptide-loaded MHC c lass II-deficient (MHC class II-/-) DC induced the activation of Ag-specifi c CD8(+) T cells and their accumulation in the lymph nodes and spleens of i mmunized mice. The accumulation induced by MHC class II-/- DC immunization was lower than the accumulation observed after immunization with MHC class II+/+ DC. Similarly, immunization with peptide-loaded, MHC class II-/- DC i nduced some degree of protection against tumor challenge, but this protecti on was lower than the protection achieved after immunization with MHC class II+/+ DC. Incubation with a membrane-associated form of CD40 ligand result ed in the up-regulation of costimulatory molecules on MHC class II-/- DC an d fully rescued their ability to induce antitumor immunity. We conclude tha t CD4(+) T cells play a critical role in the generation of antitumor immune responses through their capacity to induce the activation of DC via CD40/C D40 ligand interaction, and thus maximize CD8(+) T cell responses.