Cellular but not humoral immune responses generated by vaccination with dendritic cells protect mice against leukaemia.
Dendritic cells (DC) are extremely efficient at generating both prophylactic and therapeutic anti-tumour immunity. We aimed to analyse the respective roles of humoral and cellular immune responses generated in mice vaccinated with bone marrow (BM)-derived DC in terms of in vivo anti-leukaemia effect. We used the murine L1210 B lymphocytic leukaemia genetically modified to express on the cell surface of human CD4 (hCD4) (L1210/hCD4) as a model tumour-associated antigen (TAA). DC cultures were loaded with either purified soluble hCD4 (shCD4) protein or unfractionated L1210/hCD4 extracts and injected as vaccine into mice. The efficacy of these vaccinations was compared with that of vaccination with shCD4 protein emulsified in Freund's adjuvant (FA). We evaluated the immune responses generated after these vaccinal protocols and the survival rate of vaccinated mice subsequently challenged with a lethal injection of L1210/hCD4 cells. Our results demonstrated that vaccination with shCD4 protein or tumour extract-loaded DC mainly generated an hCD4 antigen-specific cell-mediated cytotoxic immune response that was associated with a specific protection against leukaemia. In contrast, vaccination with the protein emulsified in FA only generated potent humoral immune responses that were not protective against leukaemia. Altogether, our results indicate that the unique property of loaded DC to trigger an anti-leukaemia protective effect is mainly associated with cellular immune responses.
Colombo
B M
BM
Laboratoire de Biologie et Th¿erapeutique des Pathologies Immunitaires, ESA 7087 UP6 CNRS,H¿opital de la Piti¿e Salp¿etri¿ere, Paris, France.
Lacave
R
R
Pioche-Durieu
C
C
Masurier
C
C
Lemoine
F M
FM
Guigon
M
M
Klatzmann
D
D
D000818:Animals; D015704:CD4 Antigens / Q000008:administration & dosage / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007942:Leukemia, Experimental / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008811:Mice, Inbred DBA; D013047:Specific Pathogen-Free Organisms; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015704:CD4 Antigens; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I