Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma
| Autor: | Goldszmid, R.S., Idoyaga, J., Bravo, A.I., Steinman, R., Mordoh, J., Wainstok, R. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
melanoma cell
in vitro study cell migration dendritic cell animal experiment cell stimulation major histocompatibility antigen class 1 cell maturation animal cell cellular immunity immunogenicity tumor cell in vivo study male lymphocyte depletion T lymphocyte inoculation controlled study protein expression mouse target cell cell culture nonhuman experiment animal model apoptosis article tyrosinase related protein 2 CD8 antigen lymph node lymphatic drainage vaccination antigen recognition tumor immunity cytokine release injection priority journal provocation test cytolysis antigen expression gamma interferon CD4 antigen coculture bone marrow cell |
| Zdroj: | J. Immunol. 2003;171(11):5940-5947 Biblioteca Digital (UBA-FCEN) Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales instacron:UBA-FCEN |
| Popis: | Dendritic cells (DCs) are potent APCs and attractive vectors for cancer immunotherapy. Using the B16 melanoma, a poorly immunogenic experimental tumor that expresses low levels of MHC class I products, we investigated whether DCs loaded ex vivo with apoptotic tumor cells could elicit combined CD4+ and CD8+ T cell dependent, long term immunity following injection into mice. The bone marrow-derived DCs underwent maturation during overnight coculture with apoptotic melanoma cells. Following injection, DCs migrated to the draining lymph nodes comparably to control DCs at a level corresponding to ∼0.5% of the injected inoculum. Mice vaccinated with tumor-loaded DCs were protected against an intracutaneous challenge with B16, with 80% of the mice remaining tumor-free 12 wk after challenge. CD4+ and CD8+ T cells were efficiently primed in vaccinated animals, as evidenced by IFN-γ secretion after in vitro stimulation with DCs loaded with apoptotic B16 or DCs pulsed with the naturally expressed melanoma Ag, tyrosinase-related protein 2. In addition, B16 melanoma cells were recognized by immune CD8 + T cells in vitro, and cytolytic activity against tyrosinase-related protein 2180-188-pulsed target cells was observed in vivo. When either CD4+ or CD8+ T cells were depleted at the time of challenge, the protection was completely abrogated. Mice receiving a tumor challenge 10 wk after vaccination were also protected, consistent with the induction of tumor-specific memory. Therefore, DCs loaded with cells undergoing apoptotic death can prime melanoma-specific helper and CTLs and provide long term protection against a poorly immunogenic tumor in mice. Fil:Goldszmid, R.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Idoyaga, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|