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Start Over Author "R. Lacave" Journal immunology
3 results on '"R. Lacave"'

1. Cellular but not humoral immune responses generated by vaccination with dendritic cells protect mice against leukaemia

Author

Catherine Pioche-Durieu, David Klatzmann, C. Masurier, R. Lacave, B. M. Colombo, François M. Lemoine, and Martine Guigon

Subjects
medicine.medical_treatment, Immunology, Biology, Vaccination, medicine.anatomical_structure, Immune system, Antigen, In vivo, Immunity, medicine, Immunology and Allergy, Cytotoxic T cell, Bone marrow, Adjuvant
Abstract

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.

Published
2000
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2. Cellular but not humoral immune responses generated by vaccination with dendritic cells protect mice against leukaemia

Author

B M, Colombo, R, Lacave, C, Pioche-Durieu, C, Masurier, F M, Lemoine, M, Guigon, and D, Klatzmann

Subjects
Leukemia, Experimental, Histocompatibility Antigens Class I, Enzyme-Linked Immunosorbent Assay, Dendritic Cells, Original Articles, Flow Cytometry, Cancer Vaccines, Immunotherapy, Adoptive, Specific Pathogen-Free Organisms, Mice, Mice, Inbred DBA, CD4 Antigens, Tumor Cells, Cultured, Animals, Female, T-Lymphocytes, Cytotoxic
Abstract

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.

Published
2000

3. Immunophenotypical and functional heterogeneity of dendritic cells generated from murine bone marrow cultured with different cytokine combinations: implications for anti-tumoral cell therapy.

Author

Masurier C, Pioche-Durieu C, Colombo BM, Lacave R, Lemoine FM, Klatzmann D, and Guigon M

Subjects
Animals, Cell Differentiation immunology, Female, Granulocyte-Macrophage Colony-Stimulating Factor immunology, Histocompatibility Antigens Class II metabolism, Immunophenotyping, Interleukin-4 immunology, Leukemia L1210 prevention & control, Lymph Nodes immunology, Lymphocyte Culture Test, Mixed, Male, Membrane Proteins immunology, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Tumor Cells, Cultured, Vaccination, Bone Marrow Cells immunology, Cancer Vaccines therapeutic use, Cytokines immunology, Dendritic Cells immunology
Abstract

Dendritic cells (DC) are professional antigen-presenting cells that can be used as immune adjuvant for anti-tumoural therapies. This approach requires the generation of large quantities of DC that are fully characterized on the immunophenotypical and functional levels. In a murine model, we analysed the in vitro effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or combined with interleukin-4 (IL-4) or Flt3 ligand (Flt3-L) on the number, immunophenotype and functions of bone marrow-derived DC. In GM-CSF cultures, we have identified two populations based on their level of expression of major histocompatibility complex (MHC) class II molecules: MHC-IIhi cells, exhibiting the typical morphology and immunophenotype of myeloid DC (CD11c+ 33D1+ DEC-205+ F4/80+), and MHC-IIlo cells, heterogeneous for DC markers (30% CD11c+; 50% 33D1+; DEC-205-; F4/80+). The addition of Flt3-L to GM-CSF induced a twofold increase in MHC-IIhi DC number; besides, the MHC-IIlo cells lost all DC markers. In contrast, after addition of IL-4 to GM-CSF, the two populations displayed a very similar phenotype (CD11c+ 33D1- DEC-205+ F4/80-), differing only in their expression levels of MHC class II and costimulatory molecules, and showed similar stimulatory activity in mixed leucocyte reaction. We next analysed the migration of these cultured cells after fluorescent labelling. Twenty-four hours after injection into the footpads of mice, fluorescent cells were detected in the draining popliteal lymph nodes, with an enhanced migration when cells were cultured with GM-CSF+Flt3-L. Finally, we showed that MHC-IIhi were more efficient than MHC-IIlo cells in an anti-tumoral vaccination protocol. Altogether, our data highlight the importance of characterizing in vitro-generated DC before use in immunotherapy.

Published
1999
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