Human peripheral blood T lymphocyte proliferation after activation of the T cell receptor: effects of unsaturated fatty acids

Zurier, Robert B.; Rossetti, Ronald G.; Seiler, Christina M.; Laposata, Michael

doi:10.1016/s0952-3278(99)80015-5

Cited by 52 publications

(40 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Inhibition of stimulated IL-2R ␣-chain (CD25) expression and thus formation of the high-affinity IL-2R by PUFAs may contribute to the well-established inhibitory effect of PUFAs on T cell proliferation (22,23). Notably, expression of CD25 is regulated in a manner similar to IL-2 including binding sites for NF-AT in the promoter sequences of the respective genes (27,41).…”

Section: Discussionmentioning

confidence: 99%

Suppression of T Cell Signaling by Polyunsaturated Fatty Acids: Selectivity in Inhibition of Mitogen-Activated Protein Kinase and Nuclear Factor Activation

Zeyda¹,

Szekeres

Säemann

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

Polyunsaturated fatty acids (PUFAs) are known to suppress inflammatory and autoimmune responses and, therefore, clinical applications of PUFAs as immunomodulatory substances are extensively studied. PUFAs are known to inhibit T cell responses, but with respect to TCR/CD3-mediated signal transduction only a block in CD3-induced phospholipase Cγ1/calcium signaling has been shown so far. In this study, we investigated PUFA-mediated changes in downstream T cell signal transduction. We show that among the mitogen-activated protein kinase families activation of c-Jun NH2-terminal kinase, but not phosphorylation of extracellular signal-regulated kinase-1/-2 or p38 is inhibited. CD3/CD28-induced activity of NF-AT was markedly reduced by PUFA treatment, while activation of other nuclear receptors (AP-1 and NF-κB) remained unaltered. Furthermore, IL-2 promoter activity, IL-2 and IL-13 mRNA levels, IL-2 secretion, and IL-2R α-chain expression were significantly diminished by PUFA treatment, whereas the expression of IFN-γ, IL-4, IL-10, and CD69 remained essentially unaffected by PUFAs. In conclusion, PUFA treatment of T cells inhibits selectively c-Jun NH2-terminal kinase and NF-AT activation, resulting in diminished production of IL-2 and IL-13.

show abstract

Section: Discussionmentioning

confidence: 99%

Suppression of T Cell Signaling by Polyunsaturated Fatty Acids: Selectivity in Inhibition of Mitogen-Activated Protein Kinase and Nuclear Factor Activation

Zeyda¹,

Szekeres

Säemann

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Taken together these results indicate that the low density fractions fulfill the criteria of detergentinsoluble microdomains. Samples of each gradient fraction were then tested for PLD activity using [choline-methyl- 3 H]phosphatidylcholine, in mixed phospholipid vesicles including PIP 2 , as a substrate, in the presence or absence of rARF protein plus GTP␥S. Basal PLD activity measured in the absence of ARF plus GTP␥S was mainly present (76%) in the high density sucrose fractions, whereas the activity recovered in the low density fractions (6 -8) consisted of less than 8% of total (Fig.…”

Section: Pld1 Activity Is Located To the Detergent-insoluble Membranementioning

confidence: 99%

“…Polyunsaturated fatty acids (PUFAs) 1 are known to modulate immune response, particularly by affecting T cell function (1,2). Accordingly, dietary supplementation with n-3 fatty acids decreases the production of T cell-derived cytokines and lymphoproliferation (3,4).…”

mentioning

confidence: 99%

The Mechanism of Docosahexaenoic Acid-induced Phospholipase D Activation in Human Lymphocytes Involves Exclusion of the Enzyme from Lipid Rafts

Diaz

Berquand

Dubois

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid that inhibits T lymphocyte activation, has been shown to stimulate phospholipase D (PLD) activity in stimulated human peripheral blood mononuclear cells (PBMC). To elucidate the mechanisms underlying the DHA-induced PLD activation, we first characterized the PLD expression pattern of PBMC. We show that these cells express PLD1 and PLD2 at the protein and mRNA level and are devoid of oleate-dependent PLD activity. DHA enrichment of PBMC increased the DHA content of cell phospholipids, which was directly correlated with the extent of PLD activation. The DHA-induced PLD activation was independent of conventional protein kinase C but inhibited by brefeldin A, which suggests ADP-ribosylation factor (ARF)-dependent mechanism. Furthermore, DHA enrichment dosedependently stimulated ARF translocation to cell membranes. Whereas 50% of the guanosine 5-3-O-(thio)triphosphate plus ARF-dependent PLD activity and a substantial part of PLD1 protein were located to the detergent-insoluble membranes, so-called rafts, of nonenriched PBMC, DHA treatment strongly displaced them toward detergent-soluble membranes where ARF is present. Collectively, these results suggest that the exclusion of PLD1 from lipid rafts, due to their partial disorganization by DHA, and its relocalization in the vicinity of ARF, is responsible for its activation. This PLD activation might be responsible for the immunosuppressive effect of DHA because it is known to transmit antiproliferative signals in lymphoid cells.

show abstract

“…Among these, free fatty acids were the most abundant class of lipids identified in our samples and they proved capable of mediating the enhanced T-cell proliferation when added individually. Although some scarce reports exist with contrasting results regarding the modulatory effect of fatty acids on T-cell proliferation [15][16][17] Eur. J. Immunol.…”

mentioning

confidence: 99%

Adipocyte‐derived lipids modulate CD4⁺ T‐cell function

et al. 2013

View full text Add to dashboard Cite

Adipose tissue contains several immune cells whose number and phenotype vary depending on the adiposity. In the present study, we show that IFN-γ + CD4 + T cells are enriched in human adipose tissue compared with in blood. To gain insight into the underlying mechanisms, we investigated the possibility that human adipocytes modulate CD4 + T-cell cytokine production and proliferation and show that CD4 + T cells produced increased levels of IFN-γ when activated in the presence of adipocytes. This effect was mediated by soluble mediators, as shown in transwell and adipocyte-conditioned medium (ACM) transfer experiments. Additionally, ACM induced increased proliferation of CD4 + T cells upon activation. Intriguingly, the proliferation-enhancing effect resided mainly in the lipid fraction of ACM, as shown upon separation of the protein and lipid fraction. Further separation of these lipids based on polarity revealed that the modulatory effect is confined to fractions containing free fatty acids. All identified fatty acids were able to individually enhance T-cell proliferation. These data indicate that adipocytes can modulate CD4 + T-cell function through the release of lipids. Remarkably, free fatty acids were the most prominent modulators of T-cell proliferation, possibly leading to an accumulation of these cells in adipose tissue. Keywords: Adipocytes r CD4 + T cells r Lipids r ObesityAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionAdipose tissue is composed of adipocytes, which are primarily involved in lipid storage and release, and the stromal vascular fraction (SVF). The composition of the SVF varies, depending on the localization of the adipose tissue and the degree of adiposity of the individual, but it typically contains a large variety Correspondence: Dr. Andreea Ioan-Facsinay e-mail: A.Ioan@lumc.nl of cells, including progenitor cells, fibroblasts, endothelial cells, nerve cells, and immune cells. Among the immune cells described in adipose tissue, macrophages and T cells are the most abundant, but other cells, like NK cells, mast cells, and B cells have also been described (reviewed in [1]). While the precise role of these cells in the adipose tissue is largely unknown, there is increasing evidence that cross-talk between immune cells and adipocytes exists and that the immune cells can influence the metabolic functions of the resident adipocytes (reviewed in [1] [2,3], or local differentiation/proliferation of resident T cells [5] under the influence of the adipose tissue environment could constitute underlying mechanisms for changes in the adipose tissue CD4 + T-cell population in obesity.Adipose tissue T cells have been previously shown to be present in the vicinity of adipocytes [3]. Moreover, some adipocytederived soluble mediators, such as leptin [10, have been shown to modulate differentiation or cytokine production by CD4 + T cells. However, adipocytes can release a large number of soluble mediators with different biologica...

show abstract

Human peripheral blood T lymphocyte proliferation after activation of the T cell receptor: effects of unsaturated fatty acids

Cited by 52 publications

References 24 publications

Suppression of T Cell Signaling by Polyunsaturated Fatty Acids: Selectivity in Inhibition of Mitogen-Activated Protein Kinase and Nuclear Factor Activation

Suppression of T Cell Signaling by Polyunsaturated Fatty Acids: Selectivity in Inhibition of Mitogen-Activated Protein Kinase and Nuclear Factor Activation

The Mechanism of Docosahexaenoic Acid-induced Phospholipase D Activation in Human Lymphocytes Involves Exclusion of the Enzyme from Lipid Rafts

Adipocyte‐derived lipids modulate CD4⁺ T‐cell function

Contact Info

Product

Resources

About

Human peripheral blood T lymphocyte proliferation after activation of the T cell receptor: effects of unsaturated fatty acids

Cited by 52 publications

References 24 publications

Suppression of T Cell Signaling by Polyunsaturated Fatty Acids: Selectivity in Inhibition of Mitogen-Activated Protein Kinase and Nuclear Factor Activation

Suppression of T Cell Signaling by Polyunsaturated Fatty Acids: Selectivity in Inhibition of Mitogen-Activated Protein Kinase and Nuclear Factor Activation

The Mechanism of Docosahexaenoic Acid-induced Phospholipase D Activation in Human Lymphocytes Involves Exclusion of the Enzyme from Lipid Rafts

Adipocyte‐derived lipids modulate CD4+ T‐cell function

Contact Info

Product

Resources

About

Adipocyte‐derived lipids modulate CD4⁺ T‐cell function