Functional defects of dendritic cells in patients with CD40 deficiency
Makaleler > Tam Makale · 2003
Yazarlar: Stefania Fontana, Daniele Moratto, Surinder Mangal, Maria De Francesco, William Vermi, Simona Ferrari, Fabio Facchetti, Necil KÜTÜKÇÜLER, Claudia Fiorini, Marzia Duse, Pranab K. Das, Luigi D. Notarangelo, Alessandro Plebani, Raffaele Badolato
Blood, Uluslararası, Wos, 2003, cilt 102, ss 4099-4106
DOI: 10.1182/blood-2003-04-1244
Özet
We have recently identified 2 patients with a rare autosomal recessive form of hyper IgM disease, known as HIGM3, caused by mutations in the CD40 gene. These patients had opportunistic infections observed on X-linked hyper IgM syndrome (HIGM), suggesting that the CD40-CD40 ligand interaction is important for promoting T-cell-mediated immunity. To evaluate whether innate immunity signals may substitute CD154 for inducing the maturation of dendritic cells (DCs), we analyzed monocyte-derived DCs in these patients. Monocyte-derived DCs of HIGM3 subjects on ex vivo stimulation with tumor necrosis factor-alpha (TNF-alpha) or lipopolysaccharide (LPS) combined with interferon-gamma (IFN-gamma) normally express all the markers of mature DCs, such as CD83 and DC-LAMP. However, cell surface levels of HLA-DR in mature DCs are reduced, as is costimulatory activity of these cells for allogeneic naive T cells. In addition, CD40-deficient DCs secrete lower amounts of interleukin-12 (IL-12) but larger quantities of IL-10 than control subjects. Finally, analysis of circulating plasmacytoid DCs demonstrates a normal percentage of this subset in CD40-deficient cells, but IFN-alpha secretion in response to herpes simplex virus 1 (HSV-1) infection is severely reduced in patients. These observations suggest that the severe impairment of DC maturation may contribute to the defect of T-cell-mediated immunity observed in HIGM3 patients.