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Publication : Natural Treg cells spontaneously differentiate into pathogenic helper cells in lymphopenic conditions.

First Author  Duarte JH Year  2009
Journal  Eur J Immunol Volume  39
Issue  4 Pages  948-55
PubMed ID  19291701 Mgi Jnum  J:148179
Mgi Id  MGI:3843716 Doi  10.1002/eji.200839196
Citation  Duarte JH, et al. (2009) Natural Treg cells spontaneously differentiate into pathogenic helper cells in lymphopenic conditions. Eur J Immunol 39(4):948-55
abstractText  Induction of Forkhead-box p3 (Foxp3) expression in developing T cells upon peptide-MHC encountering has been proposed to define a lineage of committed Treg cells. However, sustained expression of Foxp3 is required for Treg function and what maintains Foxp3 expression in peripheral Treg remains obscure. To address this issue, we monitored natural Treg phenotype and function upon adoptive transfer into lymphocyte-deficient mice. We first show that about 50% of Foxp3-GFP(+) Treg isolated from Foxp3(gfp) KI animals loose Foxp3 expression in severe lymphopenic conditions. We next evidence that the cytokine IL-2, either produced by co-transferred conventional T cells or administrated i.v. prevents Foxp3 downregulation. Moreover, we document that Treg that lost Foxp3 expression upon adoptive transfer produce IL-2 are not suppressive and promote tissue infiltration and damage upon secondary transfer into alymphoid mice. Our findings that Treg convert into pathogenic Th cells in absence of IL-2 provide new clues to the success of Treg-based immune therapies.
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