Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.
John H. Kehrl,Lalage M. Wakefield,Anita B. Roberts,Sonia B. Jakowlew,Melchor Alvarez-Mon,Rik Derynck,Michael B. Sporn,Anthony S. Fauci +7 more
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TLDR
TGF-beta may be an important antigen-nonspecific regulator of human T cell proliferation, and important in T cell interaction with other cell types whose cellular functions are modulated by TGF- beta.Abstract:
This study examines the potential role of transforming growth factor beta (TGF-beta) in the regulation of human T lymphocyte proliferation, and proposes that TGF-beta is an important autoregulatory lymphokine that limits T lymphocyte clonal expansion, and that TGF-beta production by T lymphocytes is important in T cell interactions with other cell types. TGF-beta was shown to inhibit IL-2-dependent T cell proliferation. The addition of picograms amounts of TGF-beta to cultures of IL-2-stimulated human T lymphocytes suppressed DNA synthesis by 60-80%. A potential mechanism of this inhibition was found. TGF-beta inhibited IL-2-induced upregulation of the IL-2 and transferrin receptors. Specific high-affinity receptors for TGF-beta were found both on resting and activated T cells. Cellular activation was shown to result in a five- to sixfold increase in the number of TGF-beta receptors on a per cell basis, without a change in the affinity of the receptor. Finally, the observations that activated T cells produce TGF-beta mRNA and that TGF-beta biologic activity is present in supernatants conditioned by activated T cells is strong evidence that T cells themselves are a source of TGF-beta. Resting T cells were found to have low to undetectable levels of TGF-beta mRNA, while PHA activation resulted in a rapid increase in TGF-beta mRNA levels (within 2 h). Both T4 and T8 lymphocytes were found to make mRNA for TGF-beta upon activation. Using both a soft agar assay and a competitive binding assay, TGF-beta biologic activity was found in supernatants conditioned by T cells; T cell activation resulted in a 10-50-fold increase in TGF-beta production. Thus, TGF-beta may be an important antigen-nonspecific regulator of human T cell proliferation, and important in T cell interaction with other cell types whose cellular functions are modulated by TGF-beta.read more
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Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation
TL;DR: The production of TGF-beta1 is under genetic control, and this in turn influences the development of lung fibrosis, and the TGF -beta1 genotype has prognostic significance in transplant recipients.
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TGF-β Activation and Function in Immunity
Mark A. Travis,Dean Sheppard +1 more
TL;DR: This review highlights some of the important functional roles for TGF-β in immunity, focusing on its context-specific roles in either dampening or promoting T cell responses, with a focus on the key roles for members of the integrin family.
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Transforming growth factor β1 inhibits expression of NKp30 and NKG2D receptors: Consequences for the NK-mediated killing of dendritic cells
Roberta Castriconi,Claudia Cantoni,Mariella Della Chiesa,Massimo Vitale,Emanuela Marcenaro,Romana Conte,Roberto Biassoni,Cristina Bottino,Lorenzo Moretta,Alessandro Moretta +9 more
TL;DR: It is shown that transforming growth factor β1 down-regulates the surface expression of NKp30 and in part of NKG2D but not that of other triggering receptors such as NKp46, suggesting a possible mechanism by which TGFβ1-producing dendritic cells may acquire resistance to the NK-mediated attack.
Journal ArticleDOI
IL-2 Is Essential for TGF-β to Convert Naive CD4+CD25− Cells to CD25+Foxp3+ Regulatory T Cells and for Expansion of These Cells
TL;DR: The role of IL-2 on the generation of peripheral regulatory CD4+ cells is indirect and is nonredundant, but IL-4, IL-7, and IL-15, other common γ-chain cytokines, could sustain Foxp3 expression.
Journal ArticleDOI
A nuclear factor 1 binding site mediates the transcriptional activation of a type I collagen promoter by transforming growth factor-β
Pellegrino Rossi,Gerard Karsenty,Roberts Ab,Nanette S. Roche,Michael B. Sporn,Benoit de Crombrugghe +5 more
TL;DR: Using DNA transfection, it is shown that TGF-beta stimulates the activity of the mouse alpha 2(l) collagen promoter 5- to 10-fold in mouse NIH 3T3 and rat osteosarcoma cells.
References
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Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro.
Anita B. Roberts,Michael B. Sporn,Richard K. Assoian,J M Smith,Nanette S. Roche,Lalage M. Wakefield,U. Heine,Lance A. Liotta,Vincent Falanga,John H. Kehrl +9 more
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Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells.
Rik Derynck,Julie A. Jarrett,Ellson Y. Chen,Dennis H. Eaton,John Richard Bell,Richard K. Assoian,Anita B. Roberts,Michael B. Sporn,David V. Goeddel +8 more
TL;DR: The cDNA sequence indicates that the 112-amino acid monomeric form of the natural TGF-β homodimer is derived proteolytically from a much longer precursor polypeptide which may be secreted.
Journal ArticleDOI
Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization.
TL;DR: The results show that platelets contain a type beta transforming growth factor, which is distinct from platelet-derived growth factor and elicits 50% of its maximal biological response at concentrations less than 5 x 10(-12) M.
Journal ArticleDOI
Type beta transforming growth factor: a bifunctional regulator of cellular growth.
Anita B. Roberts,Mario A. Anzano,Lalage M. Wakefield,Nanette S. Roche,David F. Stern,Michael B. Sporn +5 more
TL;DR: The data indicate that the effects of TGF-beta on cells are not a function of the peptide itself, but rather of the total set of growth factors and their receptors that is operant in the cell at a given time.
Journal ArticleDOI
T cell growth factor receptors. Quantitation, specificity, and biological relevance
TL;DR: The results indicate that TCGF interacts with activated T cells via a receptor through which it initiates the T cell proliferative response, and the relative magnitude of T cell proliferation induced by a given concentration of TCGF closely paralleled the fraction of occupied receptor sites.
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