Retrovirally Transduced Bone Marrow-Derived Dendritic Cells Require CD4+ T Cell Help to Elicit Protective and Therapeutic Antitumor Immunity
| Autor: | De Veerman, Marijke, Heirman, Carlo, Van Meirvenne, Sonja, Devos, Sophie, Corthals, Jurgen, Moser, M., Thielemans, Kris |
|---|---|
| Přispěvatelé: | Physiology, Laboratory of Molecullar and Cellular Therapy, Vrije Universiteit Brussel |
| Rok vydání: | 1999 |
| Předmět: |
CD4-Positive T-Lymphocytes
Antigen Presentation Mice Inbred BALB C Ovalbumin Genetic Vectors Histocompatibility Antigens Class I Immunology Histocompatibility Antigens Class II Epitopes T-Lymphocyte Bone Marrow Cells Cell Separation Dendritic Cells Lymphocyte Activation Immunotherapy Adoptive Mice Inbred C57BL Mice Animals Immunology and Allergy Female Lymphocyte Culture Test Mixed Moloney murine leukemia virus Peptides Cells Cultured Bone Marrow Transplantation T-Lymphocytes Cytotoxic |
| Zdroj: | The Journal of Immunology. 162:144-151 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.162.1.144 |
| Popis: | It has been extensively documented that murine dendritic cells loaded with tumor-associated Ag (TAA)-derived peptides or protein can prime Ag-specific CD8+ cytotoxic T cells in vivo and can elicit Ag-specific immunity. Optimal presentation of TAA might be achieved by retroviral transduction of DCs allowing long term and stable expression of the TAA-peptides as well as the presentation of multiple epitopes in the context of MHC class I and/or class II molecules. Here we show that retroviral transduction of bone marrow-derived dendritic cells (DCs) with chicken OVA cDNA or the reporter gene green fluorescent protein retained their potent stimulatory capacity and that the transduced DCs could process and present the endogenously expressed OVA protein. The DCs transduced with cDNA encoding native OVA protein presented OVA-derived peptides in the context of MHC class I as well as MHC class II and induced a strong Ag-specific CTL response. DCs expressing a cytosolic form of OVA presented OVA peptides only in the context of MHC class I and failed to induce an OVA-specific CTL response in vivo when they had been cultured in the absence of exogenous protein. Immunization with retrovirally transduced DCs resulted in an Ag-specific immunity and rejection of a tumor cell challenge and a significant survival advantage in tumor-bearing mice. These results obtained in this rapidly lethal tumor model suggest that DCs transduced with TAA may be useful for tumor immunotherapy and underscore the importance of the simultaneous delivery of T cell help in the development of Ag-specific cytotoxic T-cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|