POLYUNSATURATED FATTY-ACIDS INHIBIT T-CELL SIGNAL-TRANSDUCTION BY MODIFICATION OF DETERGENT-INSOLUBLE MEMBRANE DOMAINS

Polyunsaturated fatty acids (PUFAs) exert immunosuppressive effects, b ut the molecular alterations leading to T cell inhibition are not yet elucidated. Signal transduction seems to involve detergent-resistant m embrane domains (DRMs) acting as functional rafts within the plasma me mbrane bilayer with Src family protein tyrosine kinases being attached to their cytoplasmic leaflet. Since DRMs include predominantly satura ted fatty acyl moieties, we investigated whether PUFAs could affect T cell signaling by remodeling of DRMs, Jurkat T cells cultured in PUFA- supplemented medium showed a markedly diminished calcium response when stimulated via the transmembrane CD3 complex or glycosyl phosphatidyl inositol (GPI)anchored CD59. Immunofluorescence studies indicated that CD59 but not Src family protein tyrosine kinase Lck remained in a pun ctate pattern after PUFA enrichment. Analysis of DRMs revealed a marke d displacement of Src family kinases (Lck, Fyn) from DRMs derived from PUFA-enriched T cells compared with controls, and the presence of Lck in DRMs strictly correlated with calcium signaling. In contrast, GPI- anchored proteins (CD59, CD48) and ganglioside GM1, both residing in t he outer membrane leaflet, remained in the DRM fraction. In conclusion , PUFA enrichment selectively modifies the cytoplasmic layer of DRMs a nd this alteration could underlie the inhibition of T cell signal tran sduction by PUFAs.