Inhibition of the CD8 T cell response and cytotoxicity by human intravenous immunoglobulin. (P5023)

Abstract

Abstract Intravenous immunoglobulin (IVIg) is made of plasma-derived human IgG and exerts anti-inflammatory effects in several autoimmune disorders when administered at high doses. The constant increase in its use exposes providers and patients to considerable risks of shortage. Understanding its complex mechanisms of action is required in order to develop potent substitutes. Our group previously demonstrated that IVIg inhibits the in vitro and in vivo activation of CD4 T cells (Aubin et al, Blood 2010), as well as the in vitro CD8 T cell activation (Trépanier et al, Blood 2012). In the present work, we investigated whether IVIg could also interfere with the CD8 T cell response, which contribute to the persistence and severity of many autoimmune conditions. Bone marrow-derived DC from C57BL/6 mice were treated with IVIg and used to cross-present ovalbumin to OVA-specific OT-I CD8 T cells. Proliferation and cytokine production were measured after 72 hours. Cytotoxicity was measured using SIINFEKL-pulsed EL-4 target cells in presence of therapeutic doses of IVIg. Results showed a reduced (50%) CD8 T cells activation in the presence of IVIg and a concomitant decrease in IL-2 and IFN-gamma secretion. In addition, IVIg-treated CD8 T cells are less cytotoxic, as measured by specific lysis of target cells. These results support a novel immunomodulatory mechanism by which IVIg decrease CD8 T cell response. The importance of these results in vivo are currently being investigated.