Induction of Antigen-Specific Regulatory T Cells following Overexpression of a Notch Ligand by Human B Lymphocytes

• Stéphane Vigouroux

  Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas

• Eric Yvon

  Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas

• Hans-Joachim Wagner

  Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas

• Ettore Biagi

  Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas

• Gianpietro Dotti

  Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas

• Uluhan Sili

  Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas

• Cecilia Lira

  Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas

• Cliona M. Rooney

  Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas

• Malcolm K. Brenner

  Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas

抄録

In mice, activation of the Notch pathway in T cells by antigen-presenting cells overexpressing Notch ligands favors differentiation of regulatory T lymphocytes responsible for antigen-specific tolerance. To determine whether this mechanism operates in human T cells, we used Epstein-Barr virus-positive lymphoblastoid cell lines (EBV-LCL) as our (viral) antigen-presenting cells and overexpressed the Notch ligand Jagged-1 (EBV-LCL J1) by adenoviral transduction. The EBV-LCL J1s were cocultured with autologous T cells, and the proliferative and cytotoxic responses to EBV antigens were measured. Transduction had no effect on EBV-LCL expression of major histocompatibility complex (MHC) antigens or of costimulatory molecules CD80, CD86, and CD40. However, we observed a 35% inhibition of proliferation and a >65% reduction in cytotoxic-T-cell activity, and interleukin 10 production was increased ninefold. These EBV-LCL J1-stimulated T lymphocytes act as antigen-specific regulatory cells, since their addition to fresh autologous T cells cultured with autologous nontransduced EBV-LCL cells significantly inhibited both proliferation and cytotoxic effector function. Within the inhibitory population, CD4 + CD25 + and CD8 + CD25 − T cells had the greatest activity. This inhibition appears to be antigen-specific, since responses to Candida and cytomegalovirus antigens were unaffected. Hence, transgenic expression of Jagged-1 by antigen-presenting cells can induce antigen-specific regulatory T cells in humans and modify immune responses to viral antigens.

収録刊行物

• Journal of Virology

  Journal of Virology 77 (20), 10872-10880, 2003-10-15

  American Society for Microbiology

キーワード

• Virology
• Insect Science
• Immunology
• Microbiology

詳細情報

• CRID: 1360292619067502592
• NII論文ID: 30020798657
• DOI: 10.1128/jvi.77.20.10872-10880.2003
• ISSN: 10985514
• ISSN: 0022538X
• Web Site: https://journals.asm.org/doi/pdf/10.1128/JVI.77.20.10872-10880.2003
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