IVIG effects on immature dendritic cells of Common Variable Immunodeficiency Patients

Abstract

Previous studies have suggested that lyophilized IGIV may inhibit dendritic cell (DC) maturation. We investigated the effects of a newer liquid formulation of IGIV on the peripheral blood monocyte (PBMC)-induced differentiation and function of DC in healthy subjects and CVID patients. Immature DCs were derived from PBMC by negative selection using magnetic beads from five adult CVID patients and six adult healthy subjects. PBMC were incubated with IL-4 and GM-CSF to induce DC maturation. IGIV (0.15 mM Gamunex), DMSO, or BSA was added to cultures. Flow cytometry was performed to analyze the differentiation of PBMC into immature DC using the following monoclonal antibodies: CD14, CD1a, CD40, CD83, CD80, CD86, HLA-DR. DC function was evaluated by lucifer yellow and dextran sulfate for antigen uptake, and allogeneic T-cell responses in mixed lymphocyte culture (MLC) assay for antigen processing. There were no significant differences in the expression of immature DC markers between controls vs. CVID patients. IGIV upregulated CD86 expression (p < 0.001) and CD83 (p < 0.001) in both groups. IGIV suppressed lucifer yellow uptake of imDC but enhanced allogeneic T-cell proliferation in MLC. We were unable to identify any defects in the DC differentiation pathway of PBMC in our CVID patients. Our results suggest that liquid 10% IGIV promotes monocyte-derived DC maturation in vitro to a more mature functional phenotype, in contrast to lyophilized IGIV, as shown by the upregulation of CD83 and CD86, and the enhanced antigen processing ability in MLC.