Bacchetta, Rosa and Gregori, Silvia and Serafini, Giorgia and Sartirana, Claudia and Schulz, Ute and Zino, Elisabetta and Tomiuk, Stefan and Jansen, Uwe and Ponzoni, Maurilio and Paties, Carlo Terenzio and Fleischhauer, Katharina and Roncarolo, Maria Grazia (2010) Molecular and functional characterization of allogantigen-specific anergic T cells suitable for cell therapy. HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 95 (12). pp. 2134-2143. ISSN 0390-6078, 1592-8721
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR-BETA; REGULATORY TYPE-1 CELLS; DENDRITIC CELLS; INTERLEUKIN-10; DIFFERENTIATION; IL-10; TRANSPLANTATION; TOLERANCE; RESPONSES; MARROW; regulatory T cells; immune responses; exogenous recombinant human IL-10 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Jul 2020 09:28 |
| Last Modified: | 06 Jul 2020 09:28 |
| URI: | https://pred.uni-regensburg.de/id/eprint/23792 |
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