The Effect of Phosphatidylserine on T Cell and Dendritic Cell Function (90.2)

Abstract

Abstract Phosphatidylserine (PS) is a phospholipid of plasma membrane. PS is located in the inner leaflet of plasma membrane but turns to outer leaflet when cell death program is initiated. It has been demonstrated that PS on apoptotic cells plays an important role in modulating immune responses. However, whether apoptotic cells release soluble PS which may subsequently affect immunocytes is not known. Recently, we found that apoptotic cells released soluble PS to the culture media which could block the binding of anti-PS antibody to apoptotic cells. To address how soluble PS influences T cell and dendritic cell function, we examined the effect of water-soluble PS (Avanti Polar Lipids, >95% purity with no endotoxin) on T cell proliferation, and monocyte-derived dendritic cell (DC) cytokine and chemokine production. Our results demonstrated that PS suppressed T cell proliferation in a significant dose-dependent manner. However, PS appeared not affecting T cell early activation based on the normal up-regulation of CD69. On DCs, PS did not induce any cytokine or chemokine production. However, PS significantly altered LPS-stimulated DC cytokine and chemokine producing profiles. We found that PS enhanced LPS-induced IL-1beta, IL-alpha, GM-CSF and IL-6, but suppressed IL-10, IL-12p40 as well as most chemokines tested. There was no significant influence on DC maturation. Our findings indicate that the apoptotic cells may modulate immune responses through releasing soluble PS. The mechanisms of PS effect on T cells and DCs are being investigated.