Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigen.

J Exp Med 2005 Nov 14;202(10):1375-86. Epub 2005 Nov 14.

Department of Pathology, University of California, San Francisco, School of Medicine, CA 94143, USA.

Transfer of naive antigen-specific CD4(+) T cells into lymphopenic mice that express an endogenous antigen as a systemic, secreted protein results in severe autoimmunity resembling graft-versus-host disease. T cells that respond to this endogenous antigen develop into effector cells that cause the disease. Recovery from this disease is associated with the subsequent generation of FoxP3(+)CD25(+) regulatory cells in the periphery. Both pathogenic effector cells and protective regulatory cells develop from the same antigen-specific T cell population after activation, and their generation may occur in parallel or sequentially. Interleukin (IL)-2 plays a dual role in this systemic T cell reaction. In the absence of IL-2, the acute disease is mild because of reduced T cell effector function, but a chronic and progressive disease develops late and is associated with a failure to generate FoxP3(+) regulatory T (T reg) cells in the periphery. Thus, a peripheral T cell reaction to a systemic antigen goes through a phase of effector cell-mediated pathology followed by T reg cell-mediated recovery, and both require the growth factor IL-2.

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http://www.jem.org/lookup/doi/10.1084/jem.20050855
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http://dx.doi.org/10.1084/jem.20050855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212975PMC
November 2005
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