IVIg decrease antigen-dependent T cell activation by reducing the FcγR-dependent antigen presentation ability of APC (78.36)

Abstract

Abstract Intravenous immunoglobulins (IVIg) have been shown to have anti-inflammatory effects in a variety of autoimmune diseases, but their mechanisms of action remain unclear. In autoimmune diseases, activated self-reactive T cells invade specific tissues and activate local APC which in turn present autoantigens on their surface, leading to T cell restimulation in a positive feedback loop. Although it was shown that IVIg could reduce T cell activation and modify their cytokine secretion pattern, it is still not clear whether this effect occurs following a direct interaction of IVIg with T cells or through an interference of IVIg with the ability of APC to present autoantigens. To address this question, we used an in vitro antigen presentation system using ovalbumin as model antigen, to study the effects of IVIg on antigen-mediated T cell activation. The results obtained showed that IVIg inhibited T cell activation but that this effect was the indirect consequence of a reduction in the antigen presentation ability of APC. We further showed that this inhibitory effect was not due to modulation of expression of MHC II or CD80/86 costimulatory molecules on the surface of APC and was independent of inhibitory FcγRIIb. Finally, we showed that F(ab')2 fragments of IVIg had no effect on antigen-mediated T cell activation, suggesting that IVIg must interact with activating FcγRs to mediate their inhibitory effect.