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 we 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 T cells 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.
Cunningham-Rundles
Charlotte
C
Department of Medicine, Mount Sinai Medical Center, 1425 Madison Avenue, New York, NY 10029, USA. Charlotte.Cunningham-Rundles@MSSM.edu
Radigan
Lin
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D017074:Common Variable Immunodeficiency / Q000453:epidemiology / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000172:deficiency*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged
D018664:Interleukin-12