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

Summary 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.