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Related Experiment Videos

Split tolerance in spleen chimeras

J Sprent1, M Hurd, M Schaefer

  • 1Department of Immunology, Scripps Research Institute, La Jolla, California 92037.

Journal of Immunology (Baltimore, Md. : 1950)
|February 1, 1995
PubMed
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Donor T cells develop strong tolerance to host antigens in vivo, despite standard in vitro assays showing little tolerance. This suggests in vitro tests may inaccurately predict T cell tolerance in the body.

Area of Science:

  • Immunology
  • Transplantation Immunology

Background:

  • Graft-versus-host disease (GVHD) occurs when T cells attack host tissues.
  • Paradoxically, large doses of parental spleen cells reduce GVHD in irradiated F1 mice.

Purpose of the Study:

  • To investigate if donor T cells in long-term spleen chimeras develop tolerance to host MHC antigens.
  • To compare in vivo tolerance with in vitro alloreactivity assays.

Main Methods:

  • Induction of GVHD in irradiated F1 mice with donor T cells.
  • Skin-allograft rejection studies in chimeric mice.
  • Adoptive transfer of T cells from chimeric mice to assess GVHD induction.
  • Standard in vitro alloreactivity assays.

Main Results:

Related Experiment Videos

  • Donor T cells in long-term spleen chimeras exhibited strong tolerance to host antigens, confirmed by skin graft acceptance and lack of GVHD induction.
  • CD4+ T cells showed tolerance in class II-disparate chimeras, and CD8+ T cells in class I-disparate chimeras.
  • In vitro assays demonstrated minimal or no T cell tolerance, contrasting sharply with in vivo findings.

Conclusions:

  • In vivo tolerance to host MHC antigens can be robust in T cells within long-term chimeras.
  • Standard in vitro assays for T cell alloreactivity are not precise indicators of physiological tolerance in vivo.