negative feedback regulation of t cells via interleukin-2 and foxp3 reciprocity负反馈调节t细胞通过白介素2和foxp3互惠.pdfVIP

Negative Feedback Regulation of T Cells via Interleukin-2 and FOXP3 Reciprocity Zoran Popmihajlov, Kendall A. Smith* Division of Immunology, Department of Medicine, Weill Medical College, Cornell University, New York, New York, United States of America Abstract As interleukin-2 (IL2) is central to the clonal expansion of antigen-selected T cells, we investigated the relationship between IL2 and the negative regulatory transcription factor FOXP3. We found IL2 to be responsible for T cell antigen receptor (TCR)- activated FOXP3 expression by both CD4+ and CD8+ human T cells, and as anticipated, FOXP3 expression restricted TCR- stimulated IL2 expression. However, no evidence could be found that FOXP3+ cells actively suppress IL2 expression by FOXP3- cells. These data are consistent with an IL2/FOXP3-dependent negative feedback loop that normally regulates the T cell immune response. It follows that a defect in this negative feedback loop as a result of a deficiency of either IL2 or FOXP3 will lead to a hyperproliferative autoimmune syndrome, without the necessity of invoking an active suppressive function for FOXP3+ T cells. Citation: Popmihajlov Z, Smith KA (2008) Negative Feedback Regulation of T Cells via Interleukin-2 and FOXP3 Reciprocity. PLoS ONE 3(2): e1581. doi:10.1371/ journal.pone.0001581 Editor: Derya Unutmaz, New York University School of Medicine, United States of America Received November 20, 2007; Accepted January 14, 2008; Published February 13, 2008 Copyright: 2008 Popmihajlov, Smith. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: NIAID/NIH, Belfer Foundation. Neither funding source participated in the conduct of the study, in the collection, analysis, i