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
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
The transforming growth factor-betas: past, present, and future.
TL;DR: The present volume on transforming growth factor-betas (TGF-0s) provides a summation of the current excitement in research on this family of peptides and briefly summarizes the present range of E F p studies.
Journal ArticleDOI
Cell-Intrinsic Transforming Growth Factor-β Signaling Mediates Virus-Specific CD8+ T Cell Deletion and Viral Persistence In Vivo
TL;DR: In this paper, sustained transforming growth factor-β (TGF-β) expression and phosphorylation of its signaling mediator, Smad-2, were distinctive features of virus-specific CD8 + T-cells during chronic versus acute viral infections in vivo.
Journal ArticleDOI
TGF-β: the missing link in CD4+CD25+ regulatory T cell-mediated immunosuppression
Wanjun Chen,Sharon M. Wahl +1 more
TL;DR: Collectively, multiple previously unconnected puzzle pieces are beginning to be linked into a more coherent, albeit incomplete picture of CD4 + CD25 + T cell-mediated suppression of antigen-activated T cells.
Journal ArticleDOI
Transforming growth factor beta as a virulence mechanism for Leishmania braziliensis
Aldina Barral,Manoel Barral-Netto,Elenita C. Yong,Cari E. Brownell,Twardzik Daniel R,Reed Steven G +5 more
TL;DR: It is demonstrated that TGF-beta is able to alter the course of in vitro and in vivo infections with L. braziliensis, the latter being characterized by an increase in interleukin 10, an important Th2 helper-T-cell cytokine.
Journal ArticleDOI
Elevated plasma transforming growth factor-β1 levels in breast cancer patients decrease after surgical removal of the tumor
Feng Ming Kong,Mitchell S. Anscher,Tadashi Murase,Barbara Abbott,J. D. Iglehart,Randy L. Jirtle +5 more
TL;DR: After surgical removal of the primary tumor, the plasma TGF-β1 level normalizes in the majority of patients; persistently elevated levels correlate with the presence of lymph node metastases or overt residual tumor.
References
More filters
Journal ArticleDOI
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.
Related Papers (5)
Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix.
Ronald A. Ignotz,Joan Massagué +1 more