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

• Published in: The Journal of immunology (1950) 1999-07, Vol.163 (1), p.77-81
• Main Authors: Hermans, I F, Ritchie, D S, Daish, A, Yang, J, Kehry, M R, Ronchese, F
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Viral - immunology; Carcinoma, Lewis Lung - genetics; Carcinoma, Lewis Lung - immunology; Carcinoma, Lewis Lung - prevention & control; CD40 Antigens - immunology; CD40 Antigens - metabolism; CD40 Ligand; Cell Movement - immunology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - transplantation; Histocompatibility Antigens Class II - genetics; Immunotherapy, Adoptive - methods; Ligands; Lymphocyte Activation; Lymphocytic choriomeningitis virus - immunology; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Receptors, Antigen, T-Cell, alpha-beta - genetics; T-Lymphocytes - metabolism; T-Lymphocytes - transplantation; Transgenes - immunology; Tumor Cells, Cultured
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.163.1.77

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 class II-deficient (MHC class II-/-) DC induced the activation of Ag-specific CD8+ T cells and their accumulation in the lymph nodes and spleens of immunized 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 induced some degree of protection against tumor challenge, but this protection was lower than the protection achieved after immunization with MHC class II+/+ DC. Incubation with a membrane-associated form of CD40 ligand resulted in the up-regulation of costimulatory molecules on MHC class II-/- DC and fully rescued their ability to induce antitumor immunity. We conclude that 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/CD40 ligand interaction, and thus maximize CD8+ T cell responses.