A model of suppression of the antigen-specific CD4 T cell response by regulatory CD25+CD4 T cells in vivo

Kristen M. Thorstenson, Laura Herzovi, Alexander Khoruts

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Despite intense recent interest, the suppressive mechanisms of regulatory CD25+CD4 T cells remain poorly understood. One deficiency in the field is the lack of in vivo models where the effects of regulatory CD25+CD4 T cells on antigen-specific responder T cells can be measured quantitatively. We describe one such model here. We compared responses of adoptively transferred naive wild-type antigen-specific CD4 T cells in syngeneic CD28-/- and wild-type recipient mice toward a nominal antigen. The cells exhibited a greater degree of proliferation and differentiation in CD28-/- mice and could not be rendered functionally hyporesponsive by systemic exposure to adjuvant-free antigen. The only reason we were able to find to explain this difference was the deficiency of regulatory CD25+CD4 T cells in the CD28-/- mice. Use of CD28-/- mice as adoptive transfer recipients provides a simple model that reveals the contribution of regulatory CD25+CD4 T cells in controlling antigen-driven responses in vivo.

Original languageEnglish (US)
Pages (from-to)335-342
Number of pages8
JournalInternational Immunology
Volume17
Issue number4
DOIs
StatePublished - Apr 2005

Bibliographical note

Funding Information:
We thank Marc Jenkins and Daniel Mueller for a critical review of the manuscript, and Kelly Podetz-Pedersen for technical assistance in maintaining the mouse colony. This work was supported by the NIH grant RO1-DK061961 to A.K.

Keywords

  • Cellular differentiation
  • T lymphocytes
  • Tolerance/suppression/anergy
  • Transgenic/knockout

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