Antigen-dependent Proliferation of CD4+ CD25+ Regulatory T Cells In Vivo

doi:10.1084/jem.20030315

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Published 21 July 2003. doi:10.1084/jem.20030315

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© Rockefeller University Press, 0022-1007/2003/7/249 $5.00
The Journal of Experimental Medicine, Volume 198, Number 2, 249-258

Antigen-dependent Proliferation of CD4⁺ CD25⁺ Regulatory T Cells In Vivo

Lucy S.K. Walker, Anna Chodos, Mark Eggena, Hans Dooms and Abul K. Abbas

Department of Pathology, University of California San Francisco, San Francisco, CA 94143

Address correspondence to Lucy S.K. Walker, MRC Centre for Immune Regulation, University of Birmingham Medical School, Vincent Drive, Birmingham B15 2TT, United Kingdom. Phone: 44-121-414-6854; Fax: 44-121-414-3599; E-mail: L.S.Walker{at}bham.ac.uk

The failure of CD25⁺ regulatory T cells (T_regs) to proliferateafter T cell receptor (TCR) stimulation in vitro has lead totheir classification as naturally anergic. Here we use T_regsexpressing a transgenic TCR to show that despite anergy in vitro,T_regs proliferate in response to immunization in vivo. T_regsalso proliferate and accumulate locally in response to transgenicallyexpressed tissue antigen whereas their CD25^- counterparts aredepleted at such sites. Collectively, these data suggest thatthe anergic state that characterizes CD25⁺ T_regs in vitro maynot accurately reflect their responsiveness in vivo. These observationssupport a model in which T_reg population dynamics are shapedby the local antigenic environment.

Key Words: CD4⁺ T lymphocytes • peripheral tolerance • autoantigen • regulatory T cells • autoimmunity

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Huang, X., Zhu, J., Yang, Y. (2005). Protection against Autoimmunity in Nonlymphopenic Hosts by CD4+CD25+ Regulatory T Cells Is Antigen-Specific and Requires IL-10 and TGF-{beta}. J. Immunol. 175: 4283-4291 [Abstract] [Full Text]
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Chen, W., Zhou, D., Torrealba, J. R., Waddell, T. K., Grant, D., Zhang, L. (2005). Donor Lymphocyte Infusion Induces Long-Term Donor-Specific Cardiac Xenograft Survival through Activation of Recipient Double-Negative Regulatory T Cells. J. Immunol. 175: 3409-3416 [Abstract] [Full Text]
Lu, L.-F., Gondek, D. C., Scott, Z. A., Noelle, R. J. (2005). NF{kappa}B-Inducing Kinase Deficiency Results in the Development of a Subset of Regulatory T Cells, which Shows a Hyperproliferative Activity upon Glucocorticoid-Induced TNF Receptor Family-Related Gene Stimulation. J. Immunol. 175: 1651-1657 [Abstract] [Full Text]
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