Distinct roles of prostaglandin H synthases 1 and 2 in T-cell development

Prostaglandin G and H synthases, or cyclooxygenases (COXs), catalyze the fo rmation of prostaglandins (PGs). Whereas COX-1 is diffusely expressed in ly mphoid cells in embryonic day 15.5 thymus, COX-2 expression is sparse, appa rently limited to stromal cells. By contrast, COX-2 is predominant in a sub set of medullary stromal cells in three- to five-week-old mice. The isozyme s also differ in their contributions to lymphocyte development. Thus, exper iments with selective COX-1 inhibitors in thymic lobes from normal and reco mbinase-activating gene-1 knockout mice support a role for this isoform in the transition from CD4(-)CD8(-) double-negative (DN) to CD4(+)CD8(+) doubl e-positive (DP). Concordant data were obtained in COX-I knockouts. Pharmaco logical inhibition and genetic deletion of COX-2, by contrast, support its role during early thymocyte proliferation and differentiation and, later, d uring maturation of the CD4 helper T-cell Lineage. PGE(2), but not other PG s, can rescue the effects of inhibition of either isoform, although it acts through distinct EP receptor subtypes. COX-dependent PG generation may rep resent a mechanism of thymic stromal support for T-cell development.