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Clin Immunol. 2005 May;115(2):147-53.

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

Author information

1
Department of Medicine, Mount Sinai Medical Center, 1425 Madison Avenue, New York, NY 10029, USA. Charlotte.Cunningham-Rundles@MSSM.edu

Abstract

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.

PMID:
15885637
DOI:
10.1016/j.clim.2004.12.007
[Indexed for MEDLINE]

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