Prostaglandin E2 selectively inhibits human CD4+ T cells secreting low amounts of both IL-2 and IL-4.
PGE2 is a potent inflammatory mediator with profound immune regulatory actions. The present study examined the effects of PGE2 on the activation/proliferation of CD4+ T cells using 37 cloned CD4+ T cell lines. Ten T cell clones sensitive to PGE2 and 10 T cell clones resistant to PGE2, as measured by proliferation in response to anti-CD3 Ab, were selected for comparison. It was found that the PGE2-sensitive T cells were characterized by low production (<200 pg/ml) of both IL-2 and IL-4, while PGE2-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 PGE2-inhibited proliferation, and PGE2-resistant Th1-, Th2-, and Th0-like clones became PGE2 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 PGE2-sensitive T cells was significantly lower than that in PGE2-resistant cells (mean intensity, 1.2 +/- 0.6 vs 7.8 +/- 5.7; p = 0.001). In contrast, CD45RO expression in PGE2-sensitive T cells was significantly higher that that in PGE2-resistant cells (mean intensity, 55.7 +/- 15.1 vs 33.4 +/- 12.9; p = 0.02). In summary, PGE2 predominantly suppressed CD45RA-RO+ CD4+ T cells with low secretion of both IL-2 and IL-4.
He
X
X
Research Service 151, Veterans Administration Medical Center, and Department of Medicine, University of Tennessee, Memphis, TN 38104, USA. xhe@utmem1.utmem.edu
Stuart
J M
JM
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D002999:Clone Cells / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000378:metabolism; D020033:Protein Isoforms / Q000032:analysis; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D007376:Interleukin-2; D008222:Lymphokines; D020033:Protein Isoforms; D015847:Interleukin-4; D017493:Leukocyte Common Antigens; D015232:Dinoprostone