title: Negative feedback regulation of T cells via interleukin-2 and FOXP3 reciprocity.
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.
authors.affiliation: Division of Immunology, Department of Medicine, Weill Medical College, Cornell University, New York, New York, USA.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Popmihajlov
authors.forename: Kendall A
authors.initials: KA
authors.lastname: Smith
mesh_terms: D015551:Autoimmunity; D049109:Cell Proliferation; D025461:Feedback, Physiological; D051858:Forkhead Transcription Factors / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D011948:Receptors, Antigen, T-Cell; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell