TGF-β converts apoptotic stimuli into the signal for Th9 differentiation. J Immunol 2012 May 01;188(9):4369-75
Date
03/31/2012Pubmed ID
22461692Pubmed Central ID
PMC3331903DOI
10.4049/jimmunol.1102698Scopus ID
2-s2.0-84860320611 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
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-β signaling is required for nTregs to survive PICA. Conversely, when an active form of exogenous TGF-β 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-β led to the generation of T(H)17 cells from conventional T cells. Together, the data demonstrate a novel role for TGF-β in the homeostasis of regulatory T cells and effector T cell differentiation and expansion.
Author List
Takami M, Love RB, Iwashima MMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Apoptosis Regulatory Proteins
Bcl-2-Like Protein 11
CD8-Positive T-Lymphocytes
Cell Differentiation
Cell Survival
Forkhead Box Protein O3
Forkhead Transcription Factors
Interleukin-6
Interleukin-9
Membrane Proteins
Mice
Mice, Transgenic
Proto-Oncogene Proteins
Signal Transduction
T-Lymphocytes, Helper-Inducer
Transforming Growth Factor beta
