TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells.
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.
Marie
Julien C
JC
Department of Immunology, University of Washington, Seattle, WA 98195, USA.
Letterio
John J
JJ
Gavin
Marc
M
Rudensky
Alexander Y
AY
D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D007108:Immune Tolerance / Q000276:immunology*; D007165:Immunosuppression Therapy; D051379:Mice; D008815:Mice, Inbred Strains; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000378:metabolism
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta