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International Immunology Advance Access originally published online on February 14, 2005
International Immunology 2005 17(4):335-342; doi:10.1093/intimm/dxh213
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org

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* and Alexander Khoruts

Center for Immunology and the Department of Medicine, University of Minnesota, 6-134 BSBE Building, 312 Church Street, SE Minneapolis, MN 55455, USA

Correspondence to: A. Khoruts; E-mail: khoru001{at}umn.edu

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.

Keywords: cellular differentiation, T lymphocytes, tolerance/suppression/anergy, transgenic/knockout

* These authors contributed equally to the work.

Transmitting editor: R. Flavell


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