EFFECTS OF PGE(2) UPON DIFFERENTIATION AND PROGRAMMED CELL-DEATH OF SUSPENSION-CULTURED CD4-CD8- THYMOCYTES

Recently, several works have focused on the modulation of the immune r esponse by arachidonic acid metabolites. Some of these metabolites, su ch as prostaglandins, have been shown to influence thymocyte ''educati on'' in vitro. However, the effect of one of them, prostaglandin E(2) (PGE(2)), in the education of CD4(-)CD8(-) double negative immature th ymocytes (DN cells) remained unclear. Using a flow cytometry analysis of DN cells cultured for 24 h in the presence of PGE(2), we observed, compared with DN thymocytes cultured without PGE(2), an increase in th e CD4(+)CD8(-)CD3(-) immature thymocytes and in the CD4(+)CD8(-) and C D8(+)CD4(-) mature single positive thymocytes and a decrease in the DN and CD4(high)CD8(high) double positive thymocytes. Other differentiat ion thymocyte surface markers, such as CD3, CD5, TCR alpha beta, TCR d elta gamma and HSAg, revealed an increasing number of thymocytes beari ng these first four markers and a lower expression of the HSAg. Furthe rmore, we observed an accumulation of CD4(low)CD8(low) thymocytes and an increasing proportion of hypodiploid nuclei. These two findings hav e been shown to be markers of the programmed cell death process. These findings suggest that PGE, probably acts on thymocyte differentiation through at least two distinct pathways. On the one hand, PGE, seems t o promote differentiation of DN cells into CD3(+)CD8(-)CD3(-) immature cells and drive CD4(+)CD8(+)CD3(+) thymocyte to a CD4(+)CD8(-) and CD 8(+)CD4(-) mature phenotype. On the other hand, PGE(2) is probably imp licated directly or indirectly in the increase or the acceleration of the programmed cell death process of immature CD4(+)CD8(+)CD3(+) thymo cytes, which is linked to the positive and/or negative selection.