Abstract Intravenous immunoglobulins (IVIg) are therapeutic preparations of human IgG isolated from thousands of plasma donations and are known to have anti-inflammatory effects in many autoimmune diseases. IVIg are also used as prophylactic agent to reduce episodes of allograft rejection but the mechanisms responsible for this effect remain to be determined. In the present work, we showed by using a mixed lymphocyte reaction as an in vitro model of allograft rejection and GvHD, that IVIg strongly inhibited T cell activation. To explain this inhibition, we postulated that IVIg modulated the expression of MHC II and costimulatory molecules expressed on APC and involved in antigen presentation and regulation of T cell activation. To study this hypothesis, PBMC were cultured with or without 10 mg/ml IVIg for 24 hours, followed by flow cytometry analysis of cell surface expression of 8 different molecules. Among these, the expression of 5 was significantly modulated on monocytes. IVIg decreased the expression of MHC II (50%), CD80 (80%), CD86 (52%) and L-ICOS (50%). Interestingly, preliminary results showed a 5-fold increase in the expression of PD-L1, a negative regulator of T cell activation. These results suggest that IVIg impair the presentation of allopeptides to T cells as well as induce negative signalling in these cells, leading to their reduced activation. Altogether these findings could help explain the induction of peripheral tolerance and improvement of graft survival by IVIg.