Summary Prostaglandin E2 (PGE2) is a lipid mediator that displays important immunomodulatory properties, such as polarization of cytokine production by T cells. Recent investigations have revealed that the effect of PGE2 on cytokine production is greatly influenced by external stimuli; however, it is unclear whether PGE2 plays a significant role in major histocompatibility complex‐mediated antigen‐specific T‐cell responses via binding to one of four subtypes of E prostanoid (EP) receptor alone or in combination. In the present study, we sought to determine the effect of PGE2 on antigen‐specific CD4+ T‐cell responses in humans, especially in terms of receptor specificity. We used purified protein derivative (PPD) and Cry j 1 as T helper type 1 (Th1) and Th2‐inducing antigens, respectively. We generated several different Cry j 1‐ and PPD‐specific T‐cell lines (TCLs). PGE2 significantly and dose‐dependently inhibited the proliferation and subsequent production of interleukin‐4 by Cry j 1‐specific TCLs and of interferon‐γ by PPD‐specific TCLs upon antigen stimulation. Administration of EP2 receptor agonist and EP4 receptor agonist suppressed these responses in an adenylate cyclase‐dependent manner, while EP1 and EP3 receptor agonists did not. Messenger RNA for EP2, EP3 and EP4, but not EP1, receptors were detected in Cry j 1‐ and PPD‐specific TCLs, and no differences in EP receptor expression were observed between them. Furthermore, PGE2 and EP2 receptor agonist significantly inhibited interleukin‐5 and interferon‐γ production by peripheral blood mononuclear cells in response to Cry j 1 and PPD stimulation, respectively. These results suggest that PGE2 suppresses both Th1‐ and Th2‐polarized antigen‐specific human T‐cell responses via a cAMP‐dependent EP2/EP4‐mediated pathway.

These results suggest that PGDS and PGES display an opposite and important role in the pathophysiology of CRS such as polyp formation, and more specifically, a biased expression of these synthases might contribute to the development of CRS by affecting eosinophilic inflammation.

The low-affinity IgG Fc receptor, FcgammaRIIB, displays inhibitory potential in experimental models such as autoimmune diseases. However, whether this receptor is involved in the onset of allergic diseases remains unknown. This study examines the role of FcgammaRIIB in the initiation of allergic rhinitis in mice. Repeated intranasal sensitization with Schistosoma mansoni egg antigen (SEA) induced SEA-specific IgE and marked nasal eosinophilia in high-responder BALB/c mice. FcgammaRIIB gene-deficient (-/-) BALB/c mice displayed severe eosinophilia compared with that of wild-type counterparts. However, FcgammaRIIB -/- mice conversely produced less SEA-specific IgE. The production of interleukin (IL)-4 but not of IL-5 or IFN-gamma by nasal mononuclear cells was also decreased in FcgammaRIIB -/- mice, suggesting that the exacerbation of nasal eosinophila in FcgammaRIIB -/- mice is independent of the local IL-5 levels. The findings in low responder C57BL/6 mice were similar. In addition, nasal eosinophilia in FcgammaRIIB -/- mice passively sensitized with SEA was exacerbated, and conversely, specific IgE production was inhibited after a nasal challenge. These results suggest that FcgammaRIIB plays a regulatory role in the initiation of allergic rhinitis that is independent of either mouse strain or type of sensitization.