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

Charlotte Cunningham-Rundles; Lin Radigan

doi:10.1016/j.clim.2004.12.007

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

Charlotte Cunningham-Rundles·Lin Radigan

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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.

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Adolescent Adult Aged CD4 Lymphocyte Count Case-Control Studies Common Variable Immunodeficiency Dendritic Cells Female Humans Interleukin-12 Lymphocyte Culture Test, Mixed Male Middle Aged 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.

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Charlotte Cunningham-Rundles, Lin Radigan. 2005. Deficient IL-12 and dendritic cell function in common variable immune deficiency.. https://doi.org/10.1016/j.clim.2004.12.007

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