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Published online before print February 9, 2005
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,1
* Department of Internal Medicine III and
Institute of Immunology, Medical University of Vienna, Austria; and
CeMM-Center of Molecular Medicine of the Austrian Academy of Sciences, Vienna
1 Correspondence: Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. E-mail: thomas.stulnig{at}meduniwien.ac.at
Polyunsaturated fatty acids (PUFAs) exert inhibitory effects on T cell-mediated immune responses. Activation of T cells in vivo depends on formation of an immunological synapse (IS) at the T cell/antigen-presenting cell (APC) interface. Here, we analyzed effects of PUFA treatment on the formation of the IS and APC-induced human T cell activation. In T cells treated with the PUFA eicosapentaenoic (EPA; 20:5,n-3) and arachidonic acid (20:4,n-6), stimulated by superantigen-presenting cells or APCs, relocalization to the IS of distinct molecules [F-actin, talin, leukocyte functional antigen-1
, clusters of differentiation (CD)3
] was inhibited markedly compared with cells treated with saturated fatty acid, whereas relocalization of protein kinase C
to the IS remained unaffected. CD3-induced, sustained phosphorylation of nucleotide exchange factor Vav, which controls cytoskeletal rearrangements underlying IS formation, was significantly reduced in EPA-treated Jurkat and peripheral blood T cells. In addition, T cell raft disruption by methyl-ß-cyclodextrin treatment and experiments with a chimeric linker for activation of T cell proteins, which is resistant to PUFA effects on lipid rafts, revealed modifications of lipid rafts as a crucial factor for PUFA-mediated inhibition of APC-stimulated cytoskeletal rearrangements. Furthermore, the efficiency of T cell/APC conjugate formation was significantly reduced with EPA-treated T cells, as was stimulation of CD69 expression, which is not altered following antibody-mediated T cell activation. In conclusion, PUFA treatment of T cells qualitatively and quantitatively alters IS formation, thereby extending T cell signaling defects to pathways that are not intrinsically altered in PUFA-treated T cells when stimulated by antibodies.
Key Words: antigen presentation • human • immunosuppression • signal transduction • T lymphocytes
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