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Related Experiment Videos

CD4+CD25+ regulatory cells in acquired MHC tolerance.

E H Field1, D Matesic, S Rigby

  • 1Department of Veterans Affairs Medical Center, Iowa City, Iowa 52246, USA. liz-field@icva.gov

Immunological Reviews
|November 28, 2001
PubMed
Summary

Regulatory CD4+CD25+ cells induce tolerance to foreign MHC antigens. These cells prevent the development of CD8+ T-cell responses, crucial for acquired self-tolerance.

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Area of Science:

  • Immunology
  • Transplantation Immunology

Background:

  • Self-tolerance is maintained by central and peripheral mechanisms.
  • Regulatory CD4+ T cells are key in controlling immune responses to self-antigens.
  • Neonatal exposure to foreign MHC antigens induces tolerance, serving as a model for acquired self-tolerance.

Purpose of the Study:

  • To investigate the role of regulatory CD4+ T cells in acquired tolerance to foreign MHC antigens.
  • To determine if regulatory CD4+ T cells can prevent T-cell alloreactivity.

Main Methods:

  • Adoptive transfer of spleen cells from neonatally tolerant mice into SCID recipients.
  • Assessment of skin graft rejection.
  • In vitro assays including cytotoxic T-lymphocyte assays, ELISPOT, and flow cytometry to analyze CD8+ T-cell effector function.

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Main Results:

  • Adoptive transfer of unfractionated spleen cells from tolerant mice inhibited skin graft rejection.
  • CD4+CD25+ cells from tolerant mice suppressed the development of anti-donor CD8+ T-cell responses in vitro.
  • Evidence of CD4+CD25+ regulatory cells mediating tolerance to foreign MHC.

Conclusions:

  • Regulatory CD4+CD25+ cells play a critical role in initiating and maintaining tolerance to foreign MHC antigens.
  • These regulatory cells prevent the development of CD8+ T-cell alloreactivity, contributing to acquired self-tolerance.