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Polyunsaturated fatty acids interfere with formation of the immunological synapse
Author(s) -
Geyeregger René,
Zeyda Maximilian,
Zlabinger Gerhard J.,
Waldhäusl Werner,
Stulnig Thomas M.
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1104687
Subject(s) - immunological synapse , biology , jurkat cells , t cell , microbiology and biotechnology , polyunsaturated fatty acid , lipid raft , antigen presenting cell , signal transduction , biochemistry , immune system , t cell receptor , fatty acid , immunology
Polyunsaturated fatty acids (PUAs) 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‐1α, clusters of differentiation (CD)3ɛ] was inhibited markedly compared with cells treated with saturated fatty acid, whereas relocalization of protein kinase Cθ 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‐β‐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.