Transforming Growth Factor-β Controls Development, Homeostasis, and Tolerance of T Cells by Regulatory T Cell-Dependent and -Independent Mechanisms

• Published in: Immunity (Cambridge, Mass.) Vol. 25; no. 3; pp. 455 - 471
• Main Authors: Li, Ming O., Sanjabi, Shomyseh, Flavell, Richard A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2006
• Subjects: Animals; Cell Differentiation - genetics; Cell Differentiation - immunology; CELLIMMUNO; Cells, Cultured; DEVBIO; Homeostasis - genetics; Homeostasis - immunology; Immune Tolerance - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Signal Transduction - genetics; Signal Transduction - immunology; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes, Regulatory - immunology; Transforming Growth Factor beta - deficiency; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - physiology; DEVBIO; CELLIMMUNO
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2006.07.011

The role of transforming growth factor-β (TGF-β) in inhibiting T cell functions has been studied with dominant-negative TGF-β receptor transgenic models; however, the full impact of TGF-β signaling on T cells and the mechanisms by which TGF-β signals remain poorly understood. Here we show that mice with T cell-specific deletion of TGF-β receptor II developed lethal inflammation associated with T cell activation and differentiation. In addition, TGF-β signaling positively regulated T cell development and homeostasis. Development of CD8 + T cells and NKT cells, maintenance of peripheral Foxp3-expressing regulatory T cells, and survival of CD4 + T cells all depended on TGF-β signaling. Both T helper 1 (Th1) differentiation and survival of activated CD4 + T cells required T-bet, the TGF-β-regulated transcription factor, which controlled CD122 expression and IL-15 signaling in Th1 cells. This study reveals pleiotropic functions of TGF-β signaling in T cells that may ensure a diverse and self-tolerant T cell repertoire in vivo.