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Related Experiment Videos

Adoptive immunotherapy in canine chimeras

H J Kolb1, W Günther, M Schumm

  • 1GSF-Forschungszentrum fur Umwelt und Gesundheit, Institut fur Klinische Hamatologie, Universitat Munchen, Germany.

Transplantation
|February 15, 1997
PubMed
Summary
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Delayed donor lymphocyte transfusions after bone marrow transplants can convert mixed chimerism to complete chimerism. This strategy enhances immune reactivity without causing graft-versus-host disease (GVHD) in dogs.

Area of Science:

  • Immunology
  • Hematology
  • Transplantation Medicine

Background:

  • Bone marrow transplantation (BMT) can establish chimerism and tolerance, creating conditions for adoptive immunotherapy.
  • T cells from the marrow donor are crucial for effective adoptive immunotherapy in chimeric states.

Purpose of the Study:

  • To investigate the efficacy and safety of adoptive immunotherapy using donor T cells in canine leukocyte antigen-identical littermate chimeras.
  • To determine the optimal timing for donor lymphocyte transfusions to avoid graft-versus-host disease (GVHD) while promoting chimerism and immune reconstitution.

Main Methods:

  • Induction of mixed chimerism in dogs using total body irradiation and T cell-inactivated allogeneic bone marrow cells.
  • Administration of donor lymphocyte transfusions at various time points post-BMT.

Related Experiment Videos

  • Assessment of chimerism (cytogenetic and lymphoid/myeloid), skin graft tolerance, and GVHD incidence.
  • Evaluation of immune reconstitution by measuring antibody titers against tetanus and diphtheria toxins post-transfusion.

    • Main Results:

    • Persistent mixed chimerism was achieved in most dogs, with tolerance to donor skin grafts observed.
    • Donor lymphocyte transfusions administered early (days 1-2, 21-22) resulted in fatal GVHD.
    • Transfusions delayed until day 61 or later prevented GVHD and led to conversion from mixed to complete chimerism in all treated dogs.
    • Transfused dogs exhibited enhanced immune responses to tetanus and diphtheria toxins compared to controls.

    Conclusions:

    • Delayed donor lymphocyte transfusions (≥2 months post-BMT) are a safe and effective method to convert mixed chimerism to complete chimerism without inducing GVHD.
    • This approach successfully transfers and enhances donor-derived immune reactivity, improving responses to existing and novel antigens.