title: Molecular and functional characterization of allogantigen-specific anergic T cells suitable for cell therapy.
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.
  
  
  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-β 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.
authors: San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Department of Regenerative Medicine, Stem Cells, and Gene Therapy, Milan, Italy.
authors: Rosa
authors: R
authors: Bacchetta
authors: Silvia
authors: S
authors: Gregori
authors: Giorgia
authors: G
authors: Serafini
authors: Claudia
authors: C
authors: Sartirana
authors: Ute
authors: U
authors: Schulz
authors: Elisabetta
authors: E
authors: Zino
authors: Stefan
authors: S
authors: Tomiuk
authors: Uwe
authors: U
authors: Jansen
authors: Maurilio
authors: M
authors: Ponzoni
authors: Carlo Terenzio
authors: CT
authors: Paties
authors: Katharina
authors: K
authors: Fleischhauer
authors: Maria Grazia
authors: MG
authors: Roncarolo
mesh_terms: D002176:Candida albicans / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000187:drug effects / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D013745:Tetanus Toxoid / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D007519:Isoantigens; D013745:Tetanus Toxoid; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma