Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.

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.

Expression of transforming growth factors beta-1, beta 2 and beta 3 in human bladder carcinomas

“…Similar discrepancies have already been described in the mouse embryo (Pelton et al, 1991). Differential expression seems to be caused by post-transcriptional regulation of expression through a 5' untranslated sequence in the TGF-0 mRNA (Kehrl et al, 1986;Kim et al, 1992). On the basis of our results, we conclude that neither mRNA nor protein levels found in tumour tissue provide a conclusive explanation for increased TGF-11 levels in the serum of patients with invasive bladder cancer.…”

Synovial Fluid Cytokines in Patients with Rheumatoid Arthritus or Other Arthritic Lesions

“…It is unclear why latent TGF-b levels are higher in RA-SF and if it has any effect in RA pathogenesis. High concentrations of active TGF-b inhibits proliferation of T cells and B cells, and it inhibits antibody production [36,37]. TGF-b also interferes with macrophage functions, such as IL-1 production [38].…”

Effect of decorin on overcoming the extracellular matrix barrier for oncolytic virotherapy

“…TGF-b is a well known pleiotropic cytokine that exerts immunosuppressive effects in many different ways, including the inhibition of T-cell proliferation and T-cell effector functions. 22,23 TGF-b also promotes the generation of Tregs, which results in added immunosuppression. 24 As high levels of TGF-b are produced by many types of tumors, the decorin-mediated suppression of TGF-b might contribute to the activation of an antitumor immune response, ultimately leading to better therapeutic effects in the lung metastasis model.…”