Triptolide suppresses T-lymphocyte proliferation by inhibiting interleukin-2 receptor expression, but spares interleukin-2 production and mRNA expression

The proliferation of T-lymphocytes is dependent upon their ability to synthesize and secrete the cytokine, interleukin-2, and to express cell surface receptors for interleukin-2 and transferrin. We have previously reported that certain fatty acids inhibit mitogen-stimulated T-lymphocyte proliferation. We now report that unsaturated fatty acids decrease the concentration of interleukin-2 in the culture medium of such cells by up to 45%. This suggests that unsaturated fatty acids inhibit lymphocyte proliferation by suppressing interleukin-2 production. However, lymphocyte proliferation was only partially restored by addition of exogenous interleukin-2 to cell culture medium in the presence of unsaturated fatty acids, indicating that these fatty acids also affect other processes involved in the control of proliferation. Saturated fatty acids, which also inhibit lymphocyte proliferation, did not affect the interleukin-2 concentration in the culture medium suggesting a different mechanism for their action. Neither saturated nor unsaturated fatty acids affected the expression of the interleukin-2 receptor by mitogenstimulated lymphocytes. In contrast, unsaturated fatty acids decreased expression of the transferrin receptor by up to 50%. These observations suggest that the mechanism by which unsaturated fatty acids inhibit lymphocyte proliferation involves suppression of interleukin-2 production and of transferrin receptor expression. The mechanism for the inhibitory action of saturated fatty acids is not clear.

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T lymphocyte activation in euthyroid Graves' ophthalmopathy: soluble interleukin 2 receptor release, cellular interleukin 2 receptor expression and interleukin 2 production

Acta Endocrinologica ◽

10.1530/acta.0.1200602 ◽

1989 ◽

Vol 120 (5) ◽

pp. 602-609 ◽

Cited By ~ 17

Author(s):

Kar Neng Lai ◽

Joseph C. K. Leung ◽

Chun Chung Chow ◽

Clive S. Cockram

Keyword(s):

T Lymphocyte ◽

Interleukin 2 ◽

Lymphocyte Activation ◽

Receptor Expression ◽

Pokeweed Mitogen ◽

Healthy Controls ◽

Interleukin 2 Receptor ◽

T Lymphocyte Activation ◽

Graves Ophthalmopathy ◽

Soluble Interleukin 2 Receptor

Abstract. The present study was undertaken to examine the cellular control arm of the immune response with regard to T lymphocyte proliferation in euthyroid Graves' ophthalmopathy. Twenty patients with euthyroid Graves' ophthalmopathy (7 on antithyroid drugs and 13 on no treatment) and 18 healthy controls were studied in an infection-free period. Mitogen-stimulated cellular interleukin 2 (IL2) receptor expression, soluble interleukin 2 receptor release, and interleukin 2 production, were studied in peripheral blood mononuclear cells cultured for 24 h. The cellular IL2 receptor expression and soluble IL2 receptor release did not differ between the patients and healthy controls. In contrast, IL2 production in response to pokeweed mitogen stimulation was increased in lymphocytes from patients with Graves' ophthalmopathy. The IL2 release did not correlate with the quantities of cellular and soluble IL2 receptor. The mitogen-stimulated cellular IL2 receptor expression, IL2 receptor release, and IL2 production did not differ between patients with or without carbimazole therapy. Despite a suggested role of autoreactive T cells in mediating the development and propagation of autoimmune thyroid disease, this study fails to demonstrate a defective T lymphocyte activation state in patients with Graves' ophthalmopathy during an euthyroid state.

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TGF-β1 in SP-A preparations influence immune suppressive properties of SP-A on human CD4+ T lymphocytes

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00401.2005 ◽

2006 ◽

Vol 291 (4) ◽

pp. L747-L756 ◽

Cited By ~ 24

Author(s):

Steffen Kunzmann ◽

Jo Rae Wright ◽

Wolfram Steinhilber ◽

Boris W. Kramer ◽

Kurt Blaser ◽

...

Keyword(s):

T Lymphocytes ◽

Mrna Expression ◽

Signaling Pathway ◽

T Lymphocyte ◽

Lymphocyte Proliferation ◽

Chinese Hamster Ovary Cells ◽

Smad Signaling ◽

T Lymphocyte Proliferation ◽

Smad Signaling Pathway ◽

Tgf Β1

Surfactant protein A (SP-A) and transforming growth factor-β1 (TGF-β1) have been shown to modulate the functions of different immune cells and specifically to inhibit T lymphocyte proliferation. The aim of the present study was to elucidate whether the Smad signaling pathway, which is activated by TGF-β1, also plays a role in SP-A-mediated inhibition of CD4+ T lymphocyte activation. Recombinant human SP-A1 expressed in Chinese hamster ovary cells [rSP-A1m (mammalian)], but not recombinant Baculovirus-derived rSP-A1hyp (hydroxyproline-deficient), suppressed T lymphocyte proliferation and IL-2 mRNA expression. To test whether SP-A induced Smad signaling, a Smad3/4-specific reporter gene was transfected in primary human CD4+ T lymphocytes. Only rSP-A1m, but not rSP-A1hyp, induced Smad-specific reporter genes, Smad2 phosphorylation, and Smad7 mRNA expression. The effect of rSP-A1m was mediated through the TGF-βRII and could be antagonized by anti-TGF-β1 neutralizing antibodies and sTGF-βRII. Western blot and ELISA analysis revealed that rSP-A1m, but not rSP-A1hyp, contained TGF-β1. TGF-β1 was responsible for the differences in inhibition of CD4+ T lymphocyte proliferation and activation of the Smad signaling pathway between rSP-A1m and rSP-A1hyp. After acidification, native SP-A, obtained from patients with alveolar proteinosis, also induced Smad signaling in human CD4+ T lymphocytes leading to an increased inhibition of T lymphocyte proliferation, thus indicating the presence of inactive, latent TGF-β1 in native SP-A samples. Association between SP-A and latent TGF-β1 provides a possible novel mechanism to regulate TGF-β1-mediated inflammation and fibrosis reactions in the lung but also leads to possible misinterpretation of immune-modulator functions of SP-A. Monitoring of SP-A preparations for possible TGF-β1 is essential.

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