Prostaglandin E2 at priming of naive CD4+ T cells inhibits acquisition of ability to produce IFN-gamma and IL-2, but not IL-4 and IL-5.
We investigated the effect of prostaglandin E2 on the acquisition of cytokine-producing ability by naive CD4+ T cells in human cord blood. Naive CD4+ T cells were stimulated for 3 days with mouse monoclonal anti-CD3 Ab, then washed and expanded in IL-2-containing medium for 3 more days. These activated T cells produced IL-2, IL-4, IL-5, and IFN-gamma upon stimulation with PMA and ionomycin. PGE2 added at priming of naive T cells inhibited the production of IL-2 and IFN-gamma, but not of IL-4 and IL-5, in a dose-dependent manner. This change in the cytokine production profile induced by PGE2 was maintained in T cells restimulated with anti-CD3 in the absence of PGE2, expanded by IL-2, and stimulated with PMA and ionomycin. The mRNA expression of IFN-gamma and IL-2, but not that of IL-4, was also decreased in these cells. Forskolin and dibutyryl cAMP had a similar effect. PGE2 must exist at an early stage of T cell activation to inhibit priming for IL-2 and IFN-gamma production. PGE2 also showed this effect, even in the presence of exogenous IFN-gamma, at the primary stimulation. These results indicate that PGE2 inhibits the acquisition of the ability to produce IL-2 and IFN-gamma by acting directly on naive T cells. Our results suggest that PGE2 plays a role in facilitating the development of the Th2-type cytokine production profile.
Katamura
K
K
Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
Shintaku
N
N
Yamauchi
Y
Y
Fukui
T
T
Ohshima
Y
Y
Mayumi
M
M
Furusho
K
K
D000818:Animals; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis*; D015848:Interleukin-5 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice
D017252:CD3 Complex; D007376:Interleukin-2; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma; D015232:Dinoprostone