The Roles of MHC Class II, CD40, and B7 Costimulation in CTL Induction by Plasmid DNA
| Autor: | Brian Crain, Stephen P. Schoenberger, Chih Min Tang, Amy Schubert, Kee Chan, Maripat Corr, Delphine J. Lee |
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| Rok vydání: | 2001 |
| Předmět: |
Cytotoxicity
Immunologic DNA Bacterial Injections Intradermal T cell CD40 Ligand Immunology Priming (immunology) chemical and pharmacologic phenomena Lymphocyte Activation Mice Adjuvants Immunologic Antigen Antigens CD MHC class I Vaccines DNA medicine Animals Immunology and Allergy CD40 Antigens Mice Knockout MHC class II Membrane Glycoproteins CD40 biology Histocompatibility Antigens Class II Antibodies Monoclonal Drug Synergism hemic and immune systems T-Lymphocytes Helper-Inducer MHC restriction Molecular biology Mice Inbred C57BL CTL medicine.anatomical_structure CD4 Antigens B7-1 Antigen biology.protein B7-2 Antigen Plasmids Signal Transduction T-Lymphocytes Cytotoxic |
| Zdroj: | The Journal of Immunology. 166:3061-3066 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | DNA-based vaccines generate potent CTL responses. The mechanism of T cell stimulation has been attributed to plasmid-transfected dendritic cells. These cells have also been shown to express plasmid-encoded proteins and to become activated by surface marker up-regulation. However, the increased surface expression of CD40 and B7 on these dendritic cells is insufficient to overcome the need for MHC class II-restricted CD4+ T cell help in the priming of a CTL response. In this study, MHC class II−/− mice were unable to generate a CTL response following DNA immunization. This deficit in CTL stimulation by MHC class II-deficient mice was only modestly restored with CD40-activating Ab, suggesting that there were other elements provided by MHC class II-restricted T cell help for CTL induction. CTL activity was also augmented by coinjection with a vector encoding the costimulatory ligand B7.1, but not B7.2. These data indicate that dendritic cells in plasmid DNA-injected mice require conditioning signals from MHC class II-restricted T cells that are both CD40 dependent and independent and that there are different roles for costimulatory molecules that may be involved in inducing optimal CTL activity. |
| Databáze: | OpenAIRE |
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