Intravenous immunoglobulin (IVIg) inhibits CD8 cytotoxic T-cell activation.

were involved in the care of the patients and contributed clinical samples and data. inhibition with ruxolitinib versus best available therapy for myelofibrosis.term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls. We recently reported that intravenous immunoglobulin (IVIg) interferes with the binding of ovalbumin immune complexes (OVA-IC) to phagocytic Fc␥Rs, leading to a decreased internaliza-tion inside antigen-presenting cells (APCs) and resulting in a reduced amount of antigen presented by MHC II molecules to CD4 helper T cells. 1 Consequently, the antigen-specific helper T-cell response is dampened in the presence of IVIg. In the context of autoimmune diseases, these observations suggest that IVIg treatment could decrease the presentation of self-antigens to CD4 T cells and prevent the subsequent autoantibody production. Although CD8 cytotoxic T cells play a substantial role in organ destruction in several autoimmune diseases, 2-4 the effect of IVIg on this cell compartment has not been studied so far. We hypothesized that CD8 T-cell activation could be impaired in the presence of IVIg, by a mechanism similar to that described for CD4 T-cell activation. We thus used OT-II (CD4) I-Ab–restricted OVA-specific primary T cells 5 to first confirm that the previously reported inhibitory effect of IVIg was not limited to I-Ad–restricted OVA-specific CD4 T cells (DO-11.10). 1 We also used OT-I (CD8) H2K b-restricted OVA-specific T cells 6 to determine the effect of IVIg on the ability of APCs to activate CD8 T cells by cross-presentation of OVA-IC. OT-I and OT-II cells were purified from the spleen and lymph nodes of C57BL/6-Tg(TcraTcrb)1100Mjb/J and B6.Cg-Tg(TcraTcrb)425Cbn/J mice, respectively. Bone marrow–derived dendritic cells (BMDCs) from C57BL/6 mice were prepared as previously described 1 and used as APCs to activate OT-I and OT-II cells in the presence of OVA-IC, with or without IVIg. T-cell activation was determined by flow cytometry using CD69 expression as a marker of cell activation. 7 Our results first show an increased proportion of OT-II cells expressing CD69 after OVA-IC presentation, from a background level of 3% up to 74% (Figure 1 top left and middle panels). When IVIg was present during OVA-IC presentation, the percentage of cells expressing CD69 only reached 10% (Figure 1 top right panel), indicating that OT-II cell activation was significantly impaired in the presence of IVIg. The inhibitory effect of IVIg on OT-II cell activation is thus similar to that previously observed with DO-11.10 …