T‐Cell Growth Factor

Smith, Kendall A.

doi:10.1111/j.1600-065x.1980.tb00327.x

Cited by 837 publications

(295 citation statements)

References 30 publications

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“…IL-2, the first interleukin peptide hormone discovered, is characterized by its ability to stimulate T-cell proliferation (Nowell 1960;Morgan et al 1976;Smith 1980;Gillis et al 1982;Greene et al 1984;Robb et al 1984a). Mature IL-2, a secreted glycoprotein of 133 amino acids (15.5 kDa), is a single chain polypeptide produced by T cells in response to immune stimuli mediated by the T-cell receptor (TCR) and major histocompatibility complexes (MHC) I and II (Nelson and Willerford 1998;Malek 2008).…”

Section: Ligand and Receptor Biologymentioning

confidence: 99%

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

Wilson

Arkin

2010

Current Topics in Microbiology and Immunology

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Section: Ligand and Receptor Biologymentioning

confidence: 99%

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

Wilson

Arkin

2010

Current Topics in Microbiology and Immunology

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“…The major pathway of T cell activation occurs via the interaction of appropriately processed and presented antigen with the T cell receptor (25)(26)(27). This interaction results in the expression of IL-2-R, and the synthesis and secretion of IL-2 (28,29). Once a critical number of high-affinity IL-2-R on the T cell membrane have bound ligand, DNA synthesis and cell division occurs.…”

Section: Shows the I N D U C T I O N O F Tgf-/3 M R N A In T Cells Atmentioning

confidence: 99%

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

Kehrl¹,

Wakefield²,

Roberts³

et al. 1986

The Journal of Experimental Medicine

1,479

615

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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.

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“…Thus it is unlikely that IL-1 is a major participant in the GCS response. IL-2 activity seems more restricted to the maintenance of T cell proliferation (22). There is very little evidence of a direct effect on B cells, and as with IL-1, GCS are profound inhibitors of IL-2 production (2).…”

Section: Physicochemical Characteristics Of Trf-smentioning

confidence: 99%

T cell-replacing factor for glucocorticosteroid-induced immunoglobulin production. A unique steroid-dependent cytokine.

Orson¹,

Grayson²,

Pike³

et al. 1983

The Journal of Experimental Medicine

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Glucocorticosteroids (GCS) added to otherwise unstimulated cultures of human peripheral blood mononuclear cells (PBMC) induce the synthesis and secretion of all classes of immunoglobulin. The magnitude of this response is similar to that seen with other polyclonal B cell activators such as pokeweed mitogen (PWM), and like that of PWM, the steroid effect is dependent on both T cells and monocytes. To determine the cellular target for GCS in these cultures, separated populations of T cells and non-T cells were preincubated with steroids and then recombined. No immunoglobulin was produced in any of these preincubation experiments. As a different approach to this question, supernatants were collected from various cell populations following stimulation with PWM, concanavalin A (Con A), phytohemagglutinin (PHA), alloantigens, or GCS. These supernatants were tested for their effects on GCS-induced Ig production by B cells. Supernatants from 3-d cultures of unstimulated, as well as GCS-treated, PBMC contained a T cell-replacing factor that permitted T-depleted PBMC to produce Ig upon steroid stimulation. This supernatant factor (TRF-S) could be produced in the absence of steroid stimulation, but both the factor and GCS were necessary for the induction of Ig synthesis. Production of the TRF-S required the presence of both T cells and adherent cells in culture and was found in the highest concentrations at 3-4 d of culture. Supernatants from cultures stimulated with PWM, PHA, Con A, and alloantigens did not contain detectable TRF-S activity, and TRF-S was unable to replace helper T cells for PWM-induced Ig production. TRF-S required the presence of adherent cells in the T cell-depleted responder population for its action. Further, it was effective in inducing Ig production along with GCS in the presence of a sufficient concentration of cyclosporin A to block all T cell helper activity for primary responses of PBMC to PWM or GCS. TRF-S was inactivated by trypsin treatment, heating to 56 degrees C, freezing, lyophilization, and storage at 4 degrees C for greater than 3 wk. Its molecular weight is probably 10,000 daltons or more, since TRF-S activity is not rapidly dialyzable. These experiments indicate that GCS-induced Ig production by human B cells does not require the presence of intact T cells in the cultures and therefore the steroids are not exerting their influence directly on T suppressor or T helper cells. Furthermore, they demonstrate a previously unrecognized cytokine that induces the differentiation of human B cells to Ig production in the presence of GCS.

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T‐Cell Growth Factor

Cited by 837 publications

References 30 publications

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

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

T cell-replacing factor for glucocorticosteroid-induced immunoglobulin production. A unique steroid-dependent cytokine.

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