Abstract Intravenous immunoglobulin (IVIg) is used for the treatment of an increasing number of autoimmune disorders. In the past decades, its uses increased constantly, creating a potential risk of shortage. In order to further understand the mechanisms by which IVIg exerts immunomodulatory effects, our group previously demonstrated that IVIg inhibits the in vitro CD8 T cell activation. The CD8 T cell response is known to contribute to the progression of several autoimmune diseases. Our results showed that antigen-mediated CD8 T cells activation was reduced by more than 50% (proliferation, CD69 expression) in the presence of IVIg (Trépanier et al., Blood 2012). In addition, recent results showed a decreased lytic activity of CD8 T cells in the presence of IVIg. In this work, we used an in vitro cross-presentation assay with bone marrow-derived dendritic cells (DC) from C57BL/6 mice and ovalbumin-specific CD8 T cells (OT-I) to study the mechanism by which IVIg affects cytotoxicity. Preliminary results suggest that IVIg prevents the shedding of CD62L/L-selectin from the surface of T cells. Shedding of CD62-L from the surface of cytotoxic T cells was recently shown to be linked to the acquisition of lytic activity. Therefore, the effect of IVIg observed on the expression of CD62L on the CD8 T cell surface may contribute to the decreased cytotoxicity of these cells. The elucidation of the mechanisms of immunomodulatory effects of IVIg could help to design a potent substitute.