Prostaglandin E2 selectively inhibits human CD4+ T cells secreting low amounts of both IL-2 and IL-4

PGE(2) is a potent inflammatory mediator with profound immune regulatory actions. The present study examined the effects of PGE(2) on the activation/proliferation of CD4(+) T cells using 37 cloned CD4+ T cell lines. Ten T cell clones sensitive to PGE(2) and 10 T cell clones resistant to PGE(2) as measured by proliferation in response to anti-CD3 Ab, were selected for comparison. It was found that the PGE(2)-sensitive T cells were characterized by low production (<200 pg/ml) of both IL-2 and IL-4, while PGE(2)-resistant T cells secreted high levels (>1000 pg/ml) of IL-2, IL-4, or both. The roles of IL-2 and IL-4 were confirmed by the finding that addition of exogenous lymphokines could restore PGE(2)-inhibited proliferation, and PGE(2)-resistant Th1-, Th2-, and Th0-like clones became PGE(2) sensitive when IL-2, IL-4, or both were removed using Abs specific for the respective lymphokines, In addition, we showed that the CD45RA expression in PGE(2)-sensitive T cells was significantly lower than that in PGE(2)-resistant cells (mean intensity, 1.2 +/- 0.6 vs 7.8 +/- 5.7; p = 0.001); In contrast, CD45RO expression in PGE(2)-sensitive T cells was significantly higher that that in PGE(2)-resistant cells (mean intensity, 55.7 +/- 15.1 vs 33.4 +/- 12.9; p = 0.02), In summary, PGE(2) predominantly suppressed CD45RA(-)RO(+) CD4(+) T cells with low secretion of both IL-2 and IL-4.