Antigen-reactive regulatory T cells can be expanded in vitro with monocytes and anti-CD28 and anti-CD154 antibodies.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: England NLM ID: 100895309 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-2566 (Electronic) Linking ISSN: 14653249 NLM ISO Abbreviation: Cytotherapy Subsets: MEDLINE
    • Publication Information:
      Publication: 2013- : London : Elsevier
      Original Publication: Oxford, England : ISIS Medical Media, c1999-
    • Subject Terms:
      Antibodies/*metabolism ; CD28 Antigens/*metabolism ; CD40 Ligand/*metabolism ; Monocytes/*metabolism ; T-Lymphocytes, Regulatory/*immunology; Animals ; Cell Proliferation ; Cells, Cultured ; Clone Cells ; Forkhead Transcription Factors/metabolism ; Humans ; Interferon-gamma/metabolism ; Receptors, Antigen, T-Cell/metabolism
    • Abstract:
      Background: In recent years, therapies with CD4 + CD25 high FoxP3 + regulatory T cells (Tregs) have been successfully tested in many clinical trials. The important issue regarding the use of this treatment in autoimmune conditions remains the specificity toward particular antigen, as because of epitope spread, there are usually multiple causative autoantigens to be regulated in such conditions.
      Methods: Here we show a method of generation of Tregs enriched with antigen-reactive clones that potentially covers the majority of such autoantigens. In our research, Tregs were expanded with anti-CD28 and anti-CD154 antibodies and autologous monocytes and loaded with a model peptide, such as whole insulin or insulin β chain peptide 9-23. The cells were then sorted into cells recognizing the presented antigen. The reactivity was verified with functional assays in which Tregs suppressed proliferation or interferon gamma production of autologous effector T cells (polyclonal and antigen-specific) used as responders challenged with the model peptide. Finally, we analyzed clonotype distribution and TRAV gene usage in the specific Tregs.
      Results: Altogether, the applied technique had a good yield and allowed us to obtain a Treg product enriched with a specific subset, as confirmed in the functional tests. The product consisted of many clones; nevertheless, the content of these clones was different from that found in polyclonal or unspecific Tregs.
      Conclusions: The presented technique might be used to generate populations of Tregs enriched with cells reactive to any given peptide, which can be used as a cellular therapy medicinal product in antigen-targeted therapies.
      (Copyright © 2020 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: antigen stimulation; antigen-reactive; antigen-specific; immune therapies; regulatory T cells
    • Accession Number:
      0 (Antibodies)
      0 (CD28 Antigens)
      0 (FOXP3 protein, human)
      0 (Forkhead Transcription Factors)
      0 (Receptors, Antigen, T-Cell)
      147205-72-9 (CD40 Ligand)
      82115-62-6 (Interferon-gamma)
    • Publication Date:
      Date Created: 20200812 Date Completed: 20210212 Latest Revision: 20210212
    • Publication Date:
      20221213
    • Accession Number:
      10.1016/j.jcyt.2020.07.001
    • Accession Number:
      32778404