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Reprogramming the immune system using antibodies.

Luis Graca1, Herman Waldmann

  • 1Therapeutic Immunology Group, Sir William Dunn School of Pathology, Oxfordshire, Oxford, England.

Methods in Molecular Biology (Clifton, N.J.)
|June 23, 2006
PubMed
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Dominant tolerance, mediated by CD4+ regulatory T cells, resists disruption and involves synergistic mechanisms like cell death and cytokines. This highlights a complex, overlapping system for maintaining self-tolerance.

Area of Science:

  • Immunology
  • Cellular and Molecular Immunology
  • Transplantation Immunology

Background:

  • Monoclonal antibody or co-receptor blockade induces robust dominant tolerance.
  • CD4+ regulatory T cells are key mediators of this dominant tolerance.
  • Tolerance mechanisms must be considered carefully in replete mouse models.

Purpose of the Study:

  • To discuss deletional and tolerogenic processes in antibody-induced tolerance.
  • To explore the role of CD4+CD25+ T cells in regulating T cell accumulation.
  • To examine the potential for tolerance to spread to other cell types.

Main Methods:

  • Review of existing literature on tolerance induction and mechanisms.
  • Discussion of in vivo studies involving adoptive transfer of lymphocytes.

Related Experiment Videos

  • Analysis of processes such as activation-induced cell death and cytokine signaling.
  • Main Results:

    • Dominant tolerance is resistant to breakdown by adoptive lymphocyte transfer.
    • CD4+CD25+ T cells inhibit lymphopenia-mediated T cell accumulation.
    • Tolerance involves a continuum of synergistic and overlapping mechanisms, not independent ones.

    Conclusions:

    • Self-tolerance relies on a complex interplay of multiple, overlapping mechanisms.
    • Mechanisms include activation-induced cell death, immunosuppressive cytokines, and immunoprivileged sites.
    • Tolerance can potentially spread to parenchymal cells, indicating broad regulatory effects.