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 Article
Oral tolerance to low dose beta 2-glycoprotein I : immunomodulation of experimental antiphospholipid syndrome
TL;DR: Oral tolerance induced in BALB/c mice by feeding low dose beta2-glycoprotein I has an immunomodulatory effect in experimental APS, demonstrating the importance of beta2GPI in the pathogenesis of the disease.
Journal ArticleDOI
TGF-β signaling in cancer.
TL;DR: The mechanisms and functions of TGF-β signaling during tumor progression are reviewed and the therapeutic potentials of targeting the T GF-β pathway in cancer are discussed.
Journal ArticleDOI
Pattern of disease after murine hepatitis virus strain 3 infection correlates with macrophage activation and not viral replication.
M. Pope,O Rotstein,Edward H. Cole,S Sinclair,R Parr,B Cruz,R Fingerote,Stephen Chung,R.M. Gorczynski,L. S. Fung +9 more
TL;DR: Significant differences are demonstrated in production of inflammatory mediators to MHV-3 infection in macrophages from resistant A/J and susceptible BALB/cJ mice, which may explain the marked hepatic necrosis and fibrin deposition and account for the lethality of MHv-3 in susceptible mice.
Journal Article
Transforming Growth Factor-Beta 1 (TGF-β1) Promotes IL-2 mRNA Expression Through the Up-regulation of NF-κB, AP-1 and NF-AT in EL4 Cells
TL;DR: Results show that TGF-beta1, in the absence of any additional stimuli, up-regulates the activity of key transcription factors involved in IL-2 gene expression, including NF-AT, NF-kappaB and AP-1, to help promoteIL-2 mRNA expression by EL4 cells.
Journal ArticleDOI
Clinical relevance of transforming growth factor-beta 1 in the urine of patients with hepatocellular carcinoma
Jung-Fa Tsai,Lea-Yea Chuang,Jen-Eing Jeng,Mei-Li Yang,Wen-Yu Chang,Min-Yuh Hsieh,Zu-Yau Lin,Juei-Hsiung Tsai +7 more
TL;DR: Raised urinary TGF-beta 1 was associated with HCC development, and is a predictor of poor prognosis, and a tumor marker for diagnosis and therapeutic follow-up of HCC.
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