Gammalinolenic Acid and Dihomogammalinolenic Acid Suppress the CD3-Mediated Signal Transduction Pathway in Human T Cells

Author: Vassilopoulos D.   Zurier R.B.   Rossetti R.G.   Tsokos G.C.  

Publisher: Academic Press

ISSN: 1521-6616

Source: Clinical Immunology, Vol.83, Iss.3, 1997-06, pp. : 237-244

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

Gammalinolenic acid (GLA; 18:3n6) and dihomogammalinolenic acid (DGLA; 20:3n6) suppress lymphocyte activation, and GLA administration reduces joint swelling and tenderness in rheumatoid arthritis patients with active synovitis. In an effort to dissect the mechanisms whereby GLA, DGLA, and other fatty acids influence lymphocyte function, we examined their effects on anti-CD3 monoclonal antibody (mAb)-mediated early signaling events in human T cells. Peripheral blood mononuclear cells from healthy individuals were incubated overnight at 37#°C with or without 10 mug/ml fatty acid and then loaded with the calcium binding fluorescent dye indo-1. Fatty acids did not affect the efficiency of indo-1 loading, and they did not alter cell surface membrane expression of the CD3 molecule. Anti-CD3 mAb (G19-4)-induced intracellular calcium [(Ca 2+ ) i ] changes were monitored by flow cytometry in negatively selected human T cells. The ratio of violet to blue fluorescence, which is proportional to (Ca 2+ ) i , was measured over time. Cells enriched with GLA and DGLA but not cells enriched with eicosapentaenoic acid (20:5n3) displayed a significant reduction in anti-CD3 mAb-induced early and late (Ca 2+ ) i responses. T cells loaded with GLA, DGLA, or medium alone displayed similar increases in (Ca 2+ ) i in response to the endoplasmic reticulum Ca 2+ -ATPase inhibitor thapsigargin. Anti-CD3 mAb-mediated inositol phosphate production was also diminished in GLA- and DGLA-treated cells. These experiments suggest that GLA and DGLA suppress T cell activation by interfering with early events in the signal transduction pathway.

Related content