TGF-beta1 Maintains Suppressor Function and Foxp3 Expression in CD4+CD25+ Regulatory T Cells

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2005 Apr 6

PMID 15809351

Citations 433

Authors

Julien C Marie

John J Letterio

Marc Gavin

Alexander Y Rudensky

Affiliations

Soon will be listed here.

Abstract

Transforming growth factor (TGF)-beta1 is a major pluripotential cytokine with a pronounced immunosuppressive effect and its deficiency results in lethal autoimmunity in mice. However, mechanisms of its immunosuppressive action are not completely understood. Here, we report that TGF-beta1 supports the maintenance of Foxp3 expression, regulatory function, and homeostasis in peripheral CD4(+)CD25(+) regulatory T (T reg) cells, but is not required for their thymic development. We found that in 8-10-d-old TGF-beta1-deficient mice, peripheral, but not thymic, T reg cells are significantly reduced in numbers. Moreover, our experiments suggest that a defect in TGF-beta-mediated signaling in T reg cells is associated with a decrease in Foxp3 expression and suppressor activity. Thus, our results establish an essential link between TGF-beta1 signaling in peripheral T reg cells and T reg cell maintenance in vivo.

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