TGF-β Regulation of T Cells

Abstract

Transforming growth factor β (TGF-β) is a key cytokine regulating the development, activation, proliferation, differentiation, and death of T cells. In CD4+ T cells, TGF-β maintains the quiescence and controls the activation of naive T cells. While inhibiting the differentiation and function of Th1 and Th2 cells, TGF-β promotes the differentiation of Th17 and Th9 cells. TGF-β is required for the induction of Foxp3 in naive T cells and the development of regulatory T cells. TGF-β is crucial in the differentiation of tissue-resident memory CD8+ T cells and their retention in the tissue, whereas it suppresses effector T cell function. In addition, TGF-β also regulates the generation or function of natural killer T cells, γδT cells, innate lymphoid cells, and gut intraepithelial lymphocytes. Here I highlight the major findings and recent advances in our understanding of TGF-β regulation of T cells and provide a personal perspective of the field. Expected final online publication date for the Annual Review of Immunology, Volume 41 is April 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

TGF-β blockade drives a transitional effector phenotype in T cells reversing SIV latency and decreasing SIV reservoirsin vivo

“…T cell activation leads to reduced levels of TCF1 and higher levels of TCF1 are present in T cells with higher stemness and low anabolic metabolism( 68 ). These findings suggest that TCF1 has a critical role in maintaining quiescence in immune cells likely in concert with TGF-β( 18, 61 ). Our data reveal that this link may be even more prominent and important in CD4 + T cells than in CD8 + T cells.…”

“…In contrast, in CD4 + T cells TGF-β is known to decrease TCR activation( 29, 60 ), restrict proliferation and inhibit cytotoxicity (including granzyme and perforin release) at different stage of infection in vivo( 30, 61 ). However, the role of TGF-β in the formation and preservation of CD4 + T cell memory is still unclear( 57 ).…”

Hepatocellular carcinoma: signaling pathways, targeted therapy, and immunotherapy

“…TGF‐β can inhibit the cytotoxicity of NK cells and the production of related cytokines, as well as suppress antigen presentation by DCs 264 . TGF‐β collaboratively inhibits the expression of IFN‐γ, thereby inhibiting antitumor activity of CD8 + T cells 265 . FGF19/FGFR‐mediated ETV4 increases the expression of PD‐L1 and chemokine CCL2 in HCC, leading to the accumulation of tumor‐associated macrophages (TAMs) and MDSCs, suppression of CD8 + T cell activity, and promotion of HCC metastasis 266 .…”

TGF‐β1 signaling and Smad7 control T‐cell responses in health and immune‐mediated disorders

“…TGF-β1 controls multiple aspects of innate immunity (e.g., the activation status and function of dendritic cells, macrophages, natural killer cells, B cells, and plasma cells) [15]. TGF-β1 regulates the proliferation, differentiation, and functions of CD4 + and CD8 + T cells [16][17][18] and is one of the most potent inhibitors of the differentiation and function of Th1 and Th2 cells, whereas it promotes the differentiation of follicular Th cells (Fig. 2) as discussed extensively by recent reviews [16][17][18].…”

“…TGF‐β1 regulates the proliferation, differentiation, and functions of CD4 + and CD8 + T cells [16–18] and is one of the most potent inhibitors of the differentiation and function of Th1 and Th2 cells, whereas it promotes the differentiation of follicular Th cells (Fig. 2) as discussed extensively by recent reviews [16–18].…”