Delineation of the mechanism of inhibition of human T cell activation by PGE2

Ryogi Minakuchi, Mary C. Wacholtz, Laurie S. Davis, Peter E. Lipsky

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Abstract

The capacity of PGE2 to inhibit human T cell responses was examined by investigating its effect on mitogen-induced IL-2 production and proliferation of highly purified CD4+ T cells. PGE2 inhibited both PHA and anti-CD3 induced proliferation and IL-2 production by an action directly on the responding T cell. Inhibition of IL-2 production reflected decreased accumulation of mRNA for IL-2. A variety of other cAMP elevating agents exerted similar inhibitory effects. Inhibition of proliferation could be overcome by supplemental IL-2, PMA, or the anti-CD28 mAb 9.3. Although PMA and 9.3 markedly increased the amount of IL-2 produced by mitogen-stimulated T cells, the percentage inhibition of IL-2 secretion caused by PGE2 and other cAMP elevating agents remained comparable in these costimulated cultures. Rescue of T cell DNA synthesis by these agents appeared to reflect the finding that, although PGE2 markedly inhibited IL-2 production, the absolute amount of IL-2 produced was increased sufficiently to sustain mitogen-induced proliferation. As anticipated, PGE2, forskolin, and cholera toxin increased T cell cAMP levels. The quantity of cellular cAMP generated in response to PGE2, cholera toxin, and forskolin could be inhibited by PMA or 2′,5′-dideoxyadenosine. Using these reagents, the inhibitory effects of PGE2 were found to reflect intracellular cAMP levels, but only within a very narrow range. The results indicate that by elevating cAMP levels, PGE2 inhibits human T cell IL-2 production at a point that is common to both the CD8 and CD28 signaling pathways.

Original languageEnglish (US)
Pages (from-to)2616-2625
Number of pages10
JournalJournal of Immunology
Volume145
Issue number8
StatePublished - Oct 15 1990

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Dinoprostone
Interleukin-2
T-Lymphocytes
Mitogens
Cholera Toxin
Colforsin
Dideoxyadenosine
Messenger RNA

ASJC Scopus subject areas

  • Immunology

Cite this

Minakuchi, R., Wacholtz, M. C., Davis, L. S., & Lipsky, P. E. (1990). Delineation of the mechanism of inhibition of human T cell activation by PGE2 Journal of Immunology, 145(8), 2616-2625.

Delineation of the mechanism of inhibition of human T cell activation by PGE2 . / Minakuchi, Ryogi; Wacholtz, Mary C.; Davis, Laurie S.; Lipsky, Peter E.

In: Journal of Immunology, Vol. 145, No. 8, 15.10.1990, p. 2616-2625.

Research output: Contribution to journalArticle

Minakuchi, R, Wacholtz, MC, Davis, LS & Lipsky, PE 1990, 'Delineation of the mechanism of inhibition of human T cell activation by PGE2 ', Journal of Immunology, vol. 145, no. 8, pp. 2616-2625.
Minakuchi, Ryogi ; Wacholtz, Mary C. ; Davis, Laurie S. ; Lipsky, Peter E. / Delineation of the mechanism of inhibition of human T cell activation by PGE2 In: Journal of Immunology. 1990 ; Vol. 145, No. 8. pp. 2616-2625.
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