In vivo and in vitro experiments show that polyunsaturated fatty acids (PUF
As) including eicosapentaenoic acid (EPA) inhibit mitogen- or antigen-stimu
lated proliferation of T cells in rodents and humans. However, the exact ma
nner and mechanisms by which PUFA inhibits T cell proliferation is not clea
r. In the present study, we investigated the suppressive effects of EPA, an
n-3 PUFA, on PHA stimulated human peripheral blood T cells, Our results sh
owed that EPA suppresses mitogen- or antigen-stimulated human T cell prolif
eration by at least 2 steps; step 1) EPA suppresses T cell proliferation by
inhibiting IL-2R alpha expression and IL-2 production; step 2) EPA induces
cell death of blast T cells without reducing the expression of IL-2R alpha
. We also showed that EPA selectively stimulates the cell death of blast T
cells but not resting T cells, The suppressive effect of EPA was mediated v
ia the production of reactive oxygen products, because EPA-stimulated H2O2
production and the suppressive effect of EPA was restored by addition of ca
talase or NAG. These results taken together suggest that such immunosuppres
sive effects of EPA may explain the apparent benefits of EPA-enriched diets
for patients with inflammatory disorders.