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...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 115(2005), 2 vom: 15. Mai, Seite 147-53
1. Verfasser: Cunningham-Rundles, Charlotte (VerfasserIn)
Weitere Verfasser: Radigan, Lin
Format: Aufsatz
Sprache:English
Veröffentlicht: 2005
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Interleukin-12 187348-17-0
Beschreibung
Zusammenfassung: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
Beschreibung:Date Completed 24.06.2005
Date Revised 14.11.2007
published: Print
Citation Status MEDLINE
ISSN:1521-7035