The Journal of Experimental Medicine
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Published online 10 February 2003 doi:10.1084/jem.20021387
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© Rockefeller University Press, 0022-1007/2003/2/451 $5.00
The Journal of Experimental Medicine, Volume 197, Number 4, 451-460

T Cell Regulation as a Side Effect of Homeostasis and Competition

Thomas Barthlott, George Kassiotis and Brigitta Stockinger

Division of Molecular Immunology, The National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom

Address correspondence to Dr. Brigitta Stockinger, Division of Molecular Immunology, The National Institute for Medical Research, Mill Hill, London NW7 1AA, UK. Phone: 44-208-9138604; Fax: 44-208-9138531; E-mail: bstocki{at}nimr.mrc.ac.uk

We have previously hypothesized that maintaining a balanced peripheral immune system may not be the sole responsibility of a specialized subset of T cells dedicated to immune regulation, but also a side effect of normal competition for shared resources within an intact immune system. Here we show that regulatory activity is correlated with high homeostatic expansion potential, reflecting the avidity for self-peptide:MHC complexes. Monoclonal transgenic T cells with high homeostatic expansion potential and lacking characteristics previously associated with regulatory function were able to regulate wasting disease induced by transfer of a small number of naive CD45RBhi CD4 T cells into lymphopenic hosts. Self-regulatory function is also found in the naive polyclonal T cell repertoire depleted of CD25+ T cells. T cells capable of preventing immune pathology, like the transgenic T cells, express higher than average levels of CD5, an indicator of avidity for self:MHC peptide complexes. We therefore propose that dysregulated expansion of potentially pathogenic T cells in a lymphopenic environment can be prevented by members of the naive T cell repertoire, irrespective of their specificity, as a side effect of their response to homeostatic and antigenic stimulation.

Key Words: T cell regulation • homeostasis • lymphopenia • immune pathology • CD4 T cells


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