Molecular and functional characterization of allogantigen-specific anergic T cells suitable for cell therapy
| Autor: | Carlo Terenzio Paties, Ute Schulz, Rosa Bacchetta, Claudia Sartirana, Elisabetta Zino, Silvia Gregori, Maria Grazia Roncarolo, Stefan Tomiuk, Maurilio Ponzoni, Uwe Jansen, Katharina Fleischhauer, Giorgia Serafini |
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| Přispěvatelé: | Bacchetta, R, Gregori, S, Serafini, G, Sartirana, C, Schulz, U, Zino, E, Tomiuk, S, Jansen, U, Ponzoni, Maurilio, Paties, Ct, Fleischhauer, K, Roncarolo, MARIA GRAZIA |
| Rok vydání: | 2010 |
| Předmět: |
Isoantigens
T-Lymphocytes Antigen presentation Cell- and Tissue-Based Therapy Cytomegalovirus Streptamer Biology Monocytes Interferon-gamma Interleukin 21 Transforming Growth Factor beta Candida albicans Tetanus Toxoid Humans Cytotoxic T cell IL-2 receptor Antigen-presenting cell Cells Cultured Cell Proliferation Oligonucleotide Array Sequence Analysis Clonal Anergy Gene Expression Profiling Hematology Natural killer T cell Interleukin-10 Cell biology Gene Expression Regulation Immunology Leukocytes Mononuclear Interleukin 12 Original Article Lymphocyte Culture Test Mixed T-Lymphocytes Cytotoxic |
| Zdroj: | Haematologica. 95:2134-2143 |
| ISSN: | 1592-8721 0390-6078 |
| DOI: | 10.3324/haematol.2010.025825 |
| Popis: | Background CD4(+) regulatory T cells are a specialized subset of T cells that actively control immune responses. Several experimental protocols have been used to expand natural regulatory T cells and to generate adaptive type 1 regulatory T cells for regulatory T-cell-based therapies. Design and Methods The ability of exogenous recombinant human interleukin-10 to induce alloantigen-specific anergy in T cells was investigated and compared to that of interleukin-10 derived from tolerogenic dendritic cells, in mixed lymphocyte cultures. A detailed characterization of the effector functions of the resulting anergized T cells is reported. Results Interleukin-10, whether exogenous or derived from tolerogenic dendritic cells, induces a population of alloantigen-specific T cells (interleukin-10-anergized T cells) containing type 1 regulatory T cells, which are anergic and actively suppress alloantigen-specific effector T cells present within the mixed population. Interleukin-10-induced anergy is transforming growth factor-beta independent, and is associated with a decreased frequency of alloantigen-specific cytotoxic T lymphocyte precursors, but interleukin-10-anergized T cells are still responsive to third-party, bacterial, and viral antigens. Tolerogenic dendritic cells are more powerful than exogenous interleukin-10 in generating type 1 regulatory T-cell precursors, and are also effective in the context of HLA-matched donors. Conclusions Based on these studies, we have developed an efficient and reproducible in vitro method to generate antigen-specific type 1 regulatory T-cell precursors starting from total peripheral blood cells with minimal cell manipulation and suitable for generating type 1 regulatory T cells for regulatory T-cell-based therapies. Background CD4(+) regulatory T cells are a specialized subset of T cells that actively control immune responses. Several experimental protocols have been used to expand natural regulatory T cells and to generate adaptive type 1 regulatory T cells for regulatory T-cell-based therapies. Design and Methods The ability of exogenous recombinant human interleukin-10 to induce alloantigen-specific anergy in T cells was investigated and compared to that of interleukin-10 derived from tolerogenic dendritic cells, in mixed lymphocyte cultures. A detailed characterization of the effector functions of the resulting anergized T cells is reported. Results Interleukin-10, whether exogenous or derived from tolerogenic dendritic cells, induces a population of alloantigen-specific T cells (interleukin-10-anergized T cells) containing type 1 regulatory T cells, which are anergic and actively suppress alloantigen-specific effector T cells present within the mixed population. Interleukin-10-induced anergy is transforming growth factor-beta independent, and is associated with a decreased frequency of alloantigen-specific cytotoxic T lymphocyte precursors, but interleukin-10-anergized T cells are still responsive to third-party, bacterial, and viral antigens. Tolerogenic dendritic cells are more powerful than exogenous interleukin-10 in generating type 1 regulatory T-cell precursors, and are also effective in the context of HLA-matched donors. Conclusions Based on these studies, we have developed an efficient and reproducible in vitro method to generate antigen-specific type 1 regulatory T-cell precursors starting from total peripheral blood cells with minimal cell manipulation and suitable for generating type 1 regulatory T cells for regulatory T-cell-based therapies. |
| Databáze: | OpenAIRE |
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