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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A phorbol ester-regulated ribonuclease system controlling transforming growth factor beta 1 gene expression in hematopoietic cells.
R E Wager,Richard K. Assoian +1 more
TL;DR: The results provide a new basis for understanding the long-term up-regulation of TGF-beta 1 gene expression that can accompany hematopoietic cell differentiation and establish the overall basis for control of TGR1 gene expression by activation of protein kinase C.
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Concentration of Transforming Growth Factor β2 in Aqueous Humor
TL;DR: The total transforming growth factor β2 concentration in the anterior chamber aqueous humor of 96 cataract patients with ages ranging from 17 to 88 years was measured using ELISA to investigate the changes that occur with age, change of axial length, difference of localization of opacification of theCataractous lens and complications with other eye diseases.
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TGF-Beta inhibits the in vitro induction of lymphokine-activated killing activity
Elizabeth A. Grimm,William L. Crump,April Durett,Jeane P. Hester,Sandhya Lagoo-Deenadalayan,Laurie B. Owen-Schaub +5 more
TL;DR: The data indicate that TGF-beta can be a potent inhibitor of LAK generation under standard activation conditions, but that this effect is regulated by the relative level of IL-2 and may be overcome and/or reversed in vitro.
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Mammalian ciliary-body epithelial cells in culture produce transforming growth factor-beta.
Horst Helbig,Karen L. Kittredge,Miguel Coca-Prados,Janet L. Davis,Alan G. Palestine,Robert B. Nussenblatt +5 more
TL;DR: The ciliary epithelium is capable of producing the inactive form of TGF-beta (mainly type 2) and may be a source of T GF-beta in the aqueous humor.
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Modulation of cytokine expression in mouse dendritic cell clones.
Francesca Granucci,Giampiero Girolomoni,M. B. Lutz,Maria Foti,Giulia Marconi,Paola Gnocchi,Luisa Nolli,Paola Ricciardi-Castagnoli +7 more
TL;DR: The results suggest that DC have a limited cytokine gene expression pattern compared to macrophages and are heterogenous in some functional properties.
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
TL;DR: Further data are obtained to support a role for TGF-beta as an intrinsic mediator of collagen formation: conditioned media obtained from activated human tonsillar T lymphocytes contain greatly elevated levels of T GF-beta compared tomedia obtained from unactivated lymphocytes.
Journal ArticleDOI
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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