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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Journal ArticleDOI
Transforming growth factor β regulation of cell proliferation
TL;DR: Two types of transforming growth factors (TGF) have been purified and well characterized, TGF alpha and TGF beta as discussed by the authors, and they have been shown to have growth stimulatory effects only in fibroblastic cells.
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Evaluation of transforming growth factor β and type I procollagen gene expression in fibrotic skin diseases by in situ hybridization
Juha Peltonen,Leena Kähäri,Sirkku Jaakkola,Veli-Matti Kähäri,John Varga,Jouni Uitto,Sergio A. Jimenez +6 more
TL;DR: The results suggest that TGF beta 1 may play a role in the development of skin fibrosis in cases of DF and GM, but cannot implicate TGFbeta 1 in the pathogenesis of skin Fibrosis in PSS.
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TGF-β stimulates primary human skin fibroblast DNA synthesis via an autocrine production of PDGF-related peptides
TL;DR: The data suggest that TGF‐β may stimulate the growth of fibroblastic cells via an autocrine production of PDGF‐related proteins via the expression of the PDGF A‐chain gene.
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Regulation of transforming growth factor. beta. 1 gene expression by the product of the retinoblastoma-susceptibility gene
TL;DR: It is demonstrated that human RB can regulate TGF-beta 1 gene expression negatively or positively depending on the cell type, and is shown to repress its expression in NIH 3T3 and AKR-2B mouse cells.
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Tumor evasion from T cell surveillance.
Katrin Töpfer,Stefanie Kempe,Nadja Müller,Marc Schmitz,Michael Bachmann,Marc Cartellieri,Gabriele Schackert,Achim Temme +7 more
TL;DR: The data on how tumor cells evade T-cell immune surveillance with the focus on solid tumors is summarized and approaches to improve anticancer capacity of T cells are described.
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.
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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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