Neutralization of mitogenic lectins by intravenous immunoglobulin (IVIg) prevents T cell activation: does IVIg really have a direct effect on T cells?

Intravenous immunoglobulin (IVIg) is used for the treatment of an increasing number of autoimmune diseases. Clinical observations on IVIg-treated patients have revealed a modulation of T cell populations and functions in these patients. In vitro studies aimed at understanding the mechanisms underlying the effects of IVIg on T cells led to the conclusion that IVIg directly affected lectin-activated T cell functions. However, more recent studies have suggested the absence of a direct effect of IVIg on T cells. In the present work, we revisited the effect of IVIg on T cells using lectin-stimulated human T cells and showed that IVIg inhibited T cell functions only when added simultaneously with the activating lectin. Further, we showed that IVIg depleted from lectin-reactive IgG was no longer inhibitory, suggesting that the effect of IVIg on T cells was the consequence of lectin neutralization, possibly by interaction with glycans present in F(ab')(2) portion of IgG molecules. Our results challenge the previously widely accepted notion that IVIg exerts its anti-inflammatory effects by acting directly on T cells and suggest that effects of IVIg observed in treated patients are rather a consequence of the recently reported inhibitory effect of IVIg on antigen presentation.