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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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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Gene Transfer of Transforming Growth Factor-β1 Prolongs Murine Cardiac Allograft Survival by Inhibiting Cell-Mediated Immunity
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Cytokine Regulation of Metastasis and Tumorigenicity.
TL;DR: The structure/function of several cytokine families are described and the current understanding on the roles and mechanisms of cytokines in tumor progression are reviewed to discuss strategies for exploiting the expression and activity of cytokine in therapeutic intervention.
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Immunocytochemically Detectable TGF-β Associated with Malignancy in Thyroid Epithelial Neoplasia
Bharat Jasani,F. S. Wyllie,P. A. Wright,Nicholas R. Lemoine,Williams Ed,David Wynford-Thomas +5 more
TL;DR: It is concluded that a major alteration in expression of TGF-beta occurs specifically in the malignant stage of tumor development in thyroid follicular epithelium and speculate on its possible role in this process.
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Transforming Growth Factor-β Signaling in Normal and Malignant Hematopoiesis
Iris Isufi,Mahesh Seetharam,Li Zhou,Davendra Sohal,Joanna Opalinska,Perry Pahanish,Amit Verma +6 more
TL;DR: Transforming growth factor-β (TGF-β) is an important physiologic regulator of cell growth and differentiation as mentioned in this paper and has been shown to inhibit the proliferation of quiescent hematopoietic stem cells and stimulate the differentiation of late progenitors to erythroid and myeloid cells.
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Dendritic cells and (CD4+)CD25+ T regulatory cells: crosstalk between two professionals in immunity versus tolerance.
TL;DR: This review focuses on the recent development in the understanding of DCs and (CD4+)CD25+ T regs in immune tolerance, with transforming growth factor-beta (TGF-beta) serving as a potential link between these two professionals.
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.
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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
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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.
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T cell growth factor receptors. Quantitation, specificity, and biological relevance
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