Functional defects of dendritic cells in patients with CD40 deficiency
Küçük Resim Yok
Tarih
2003
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Amer Soc Hematology
Erişim Hakkı
info:eu-repo/semantics/openAccess
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 (TNP-alpha) or lipopolysaccharide (LIPS) 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 interieukin-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. (C) 2003 by The American Society of Hematology.
Açıklama
Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and-CytokineResearch/European-Cytokine-Society/Society-for-Leukocyte-Biology -- OCT 06-10, 2002 -- TURIN, ITALY
Anahtar Kelimeler
Kaynak
Blood
WoS Q Değeri
Q1
Scopus Q Değeri
Cilt
102
Sayı
12
