TGF-beta converts apoptotic stimuli into the signal for Th9 differentiation. Journal Article

Authors: Takami, M; Love, R. B.; Iwashima, M
Article Title: TGF-beta converts apoptotic stimuli into the signal for Th9 differentiation.
Abstract: Naturally arising CD4(+)CD25(+)FoxP3(+) regulatory T cells (nTregs) have an essential role in maintenance of immune homeostasis and peripheral tolerance. Previously, we reported that conventional CD4(+) and CD8(+) T cells undergo p53-induced CD28-dependent apoptosis (PICA) when stimulated with a combination of immobilized anti-CD3 and anti-CD28 Abs, whereas nTregs expand robustly under the same conditions, suggesting that there is a differential survival mechanism against PICA between conventional T cells and nTregs. In this study, we demonstrate that TGF-beta signaling is required for nTregs to survive PICA. Conversely, when an active form of exogenous TGF-beta is present, conventional T cells become resistant to PICA and undergo robust expansion instead of apoptosis, with reduction of the proapoptotic protein Bim and FoxO3a. A substantial fraction of PICA-resistant T cells expressed IL-9 (T(H)9 cells). Moreover, the presence of IL-6 along with TGF-beta led to the generation of T(H)17 cells from conventional T cells. Together, the data demonstrate a novel role for TGF-beta in the homeostasis of regulatory T cells and effector T cell differentiation and expansion.
Journal Title: Journal of Immunology
Volume: 188
Issue: 9
ISSN: 1550-6606
Publisher: Unknown  
Journal Place: United States
Date Published: 2012
Start Page: 4369
End Page: 4375
Language: English
Notes: ID: 12363; Record Owner: From MEDLINE, a database of the U.S. National Library of Medicine.; Status: MEDLINE; Publishing Model: Journal available in: Print-Electronic Citation processed from: Internet; NLM Journal Code: ifb, 2985117r; Other ID: Source: NLM. NIHMS361412 [Available on 05/01/13] Source: NLM. PMC3331903 [Available on 05/01/13]; CAS Registry/EC Number/Name of Substance: 0 (Apoptosis Regulatory Proteins). 0 (Bcl-2-like protein 11). 0 (Forkhead Transcription Factors). 0 (FoxO3 protein, mouse). 0 (Interleukin-6). 0 (Interleukin-9). 0 (Membrane Proteins). 0 (Proto-Oncogene Proteins). 0 (Transforming Growth Factor beta).; Grant Number: R01 AI055022 (United States NIAID NIH HHS); Electronic Date of Publication: 20120328; Entry Date: 20120611