Deficient IL-12 and dendritic cell function in common variable immune deficiency

Patients with common variable immune deficiency have reduced serum IgG, IgA, and/or IgM, defective antibody production, and many have cellular abnormalities. including proliferative defects, accelerated T cell apoptosis, and insufficient production of IL-2 and IL-10. Excess monocyte intracellular IL-12 leading to a polarized Th-1-type response which could prevent antibody production has been suggested . Here -,ve found that dendritic cells (DCs) of CVID Subjects have a significantly reduced capacity to secrete IL- 12, as compared to DCs of normal subjects when cultured with physiologic simulators: LPS (P = 0.0005), TNF-alpha (P = 0.006), or- CD40-L fusion protein (P = 0.0004). CVID TNF-alpha or CD40-Ligand matured DCs were also significantly impaired in antigen presentation in mixed lymphocyte culture. Deficient IL-12 production was closely correlated to lymphocyte functions in vitro and to the absolute numbers of CD4 Tcells in peripheral blood. While CVID DCs appear morphologically similar to DCs of normal subjects, the lack of IL-12 production and defective antigen presentation demonstrate functional defects. Deficient DC function Could lead to attenuated T cell activation and defective immunization, features characteristic of CVID. (c) 2005 Elsevier Inc. All rights reserved.