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 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.
Hermans
I F
IF
Malaghan Institute of Medical Research, Wellington School of Medicine, New Zealand.
Ritchie
D S
DS
Daish
A
A
Yang
J
J
Kehry
M R
MR
Ronchese
F
F
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism*; D023201:CD40 Ligand; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D016219:Immunotherapy, Adoptive / Q000379:methods; D008024:Ligands; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism / Q000637:transplantation; D019076:Transgenes / Q000276:immunology; D014407:Tumor Cells, Cultured
D000956:Antigens, Viral; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D023201:CD40 Ligand