CD4+/CD25+ regulatory cells inhibit activation of tumor-primed CD4+ T cells with IFN-gamma-dependent antiangiogenic activity, as well as long-lasting tumor immunity elicited by peptide vaccination
| Autor: | Casares, N. (Noelia), Arribillaga, L. (Laura), Sarobe, P. (Pablo), Dotor, J. (Javier), Lopez-Diaz-de-Cerio, A. (Ascensión), Melero, I. (Ignacio), Lasarte, J.J. (Juan José) |
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| Rok vydání: | 2003 |
| Předmět: |
Interferon-gamma/physiology
Receptors Interleukin-2/biosynthesis Peptides/immunology CD4-Positive T-Lymphocytes/immunology hemic and immune systems chemical and pharmacologic phenomena Angiogenesis Inhibitors/physiology Colonic Neoplasms/immunology Down-Regulation/immunology Lymphocyte Activation/immunology T-Lymphocyte Subsets/immunology |
| Zdroj: | Dadun. Depósito Académico Digital de la Universidad de Navarra instname |
| Popis: | CD25(+) regulatory T (T reg) cells suppress the activation/proliferation of other CD4(+) or CD8(+) T cells in vitro. Also, down-regulation of CD25(+) T reg cells enhance antitumor immune responses. In this study, we show that depletion of CD25(+) T reg cells allows the host to induce both CD4(+) and CD8(+) antitumoral responses following tumor challenge. Simultaneous depletion of CD25(+) and CD8(+) cells, as well as adoptive transfer experiments, revealed that tumor-specific CD4(+) T cells, which emerged in the absence of CD25(+) T reg cells, were able to reject CT26 colon cancer cells, a MHC class II-negative tumor. The antitumoral effect mediated by CD4(+) T cells was dependent on IFN-gamma production, which exerted a potent antiangiogenic activity. The capacity of the host to mount this antitumor response is lost once the number of CD25(+) T reg cells is restored over time. However, CD25(+) T reg cell depletion before immunization with AH1 (a cytotoxic T cell determinant from CT26 tumor cells) permits the induction of a long-lasting antitumoral immune response, not observed if immunization is conducted in the presence of regulatory cells. A study of the effect of different levels of depletion of CD25(+) T reg cells before immunization with the peptide AH1 alone, or in combination with a Th determinant, unraveled that Th cells play an important role in overcoming the suppressive effect of CD25(+) T reg on the induction of long-lasting cellular immune responses. |
| Databáze: | OpenAIRE |
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