International Immunology Advance Access originally published online on January 31, 2005
International Immunology 2005 17(3):279-288; doi:10.1093/intimm/dxh207
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CD25+CD4+ T cells compete with naive CD4+ T cells for IL-2 and exploit it for the induction of IL-10 production
1 Division of Molecular Immunology, 2 Division of Immune Cell Biology and 3 Division of Immune Regulation, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
Correspondence to: B. Stockinger; E-mail: bstocki{at}nimr.mrc.ac.uk
Maintenance of homeostasis in the immune system involves competition for resources between T lymphocytes, which avoids the development of immune pathology seen in lymphopenic mice. CD25+CD4+ T cells are important for homeostasis, but there is as yet no consensus on their mechanisms of action. Although CD25+CD4+ T cells cause substantial down-regulation of IL-2 mRNA in responder T cells in an in vitro co-culture system, the presence of IL- protein can be demonstrated by intracellular staining. As a consequence of competition for IL-2, CD25+CD4+ T cells further up-regulate the IL-2R 
chain (CD25), a process that is strictly dependent on IL-2, whereas responder T cells fail to up-regulate CD25. Similarly, adoptive transfer into lymphopenic mice showed that CD25+CD4+ T cells interfere with CD25 up-regulation on co-transferred naive T cells, while increasing their own CD25 levels. IL-2 sequestration by CD25+CD4+ T cells is not a passive phenomenon but instead initiates—in conjunction with signals through the TCR—their differentiation to IL-10 production. Although IL-10 is not required for in vitro suppression, it is vital for the in vivo function of regulatory T cells. Our data provide a link explaining the apparent difference in regulatory mechanisms in vitro and in vivo.
Keywords: CD25 regulation, homeostasis, IL-10, regulatory T cells, suppression
Transmitting editor: E. Simpson
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