Prostaglandin E2 and IL-4 provide naive CD4+ T cells with distinct inhibitory signals for the priming of IFN-gamma production.
We investigated the effects of prostaglandin E2 and IL-4 on the acquisition of cytokine-producing ability by naive CD4(+) T cells in human umbilical cord blood. The presence of PGE2 or IL-4 at primary stimulation inhibited the production of IFN-gamma at secondary stimulation, and the combination of these stimuli resulted in cooperative effects. During primary stimulation with anti-CD3, the intracellular cAMP level was elevated in PGE2-treated cells but not in IL-4-treated or control cells. The signal provided by PGE2, but not by IL-4, was inhibited with RpcAMP, indicating that it was mediated by cAMP. After differentiation into Th2-like cells, cAMP levels in PGE2- and IL-4-treated cells were not different. Our results suggest that both PGE2 and IL-4 play important roles with distinct mechanisms in inhibiting the priming of IFN-gamma production of naive CD4(+) T cells.
Abe
N
N
Faculty of Medicine, Kyoto University, Kyoto, 606, Japan.
Katamura
K
K
Shintaku
N
N
Fukui
T
T
Kiyomasu
T
T
Iio
J
J
Ueno
H
H
Tai
G
G
Mayumi
M
M
Furusho
K
K
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D015232:Dinoprostone / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D015847:Interleukin-4; D007371:Interferon-gamma; D015232:Dinoprostone