Effects of PGE2 upon differentiation and programmed cell death of suspension cultured CD4-CD8- thymocytes

Recently, several works have focused on the modulation of the immune response by arachidonic acid metabolites. Some of these metabolites, such as prostaglandins, have been shown to influence thymocyte "education" in vitro. However, the effect of one of them, prostaglandin E2 (PGE2), in the education of CD4-CD8- double negative immature thymocytes (DN cells) remained unclear. Using a flow cytometry analysis of DN cells cultured for 24 h in the presence of PGE2, we observed, compared with DN thymocytes cultured without PGE2, an increase in the CD4+CD8-CD3- immature thymocytes and in the CD4+CD8- and CD8+CD4- mature single positive thymocytes and a decrease in the DN and CD4highCD8high double positive thymocytes. Other differentiation thymocyte surface markers, such as CD3, CD5, TCR alpha beta, TCR delta gamma and HSAg, revealed an increasing number of thymocytes bearing these first four markers and a lower expression of the HSAg. Furthermore, we observed an accumulation of CD4lowCD8low thymocytes and an increasing proportion of hypodiploid nuclei. These two findings have been shown to be markers of the programmed cell death process. These findings suggest that PGE2 probably acts on thymocyte differentiation through at least two distinct pathways. On the one hand, PGE2 seems to promote differentiation of DN cells into CD4+CD8-CD3- immature cells and drive CD4+CD8+CD3+ thymocyte to a CD4+CD8- and CD8+CD4- mature phenotype. On the other hand, PGE2 is probably implicated directly or indirectly in the increase or the acceleration of the programmed cell death process of immature CD4+CD8+CD3+ thymocytes, which is linked to the positive and/or negative selection.