Defective maturation of dendritic cells in common variable immunodeficiency
Autor: | A. D. B. Webster, Sarita Workman, M. Raeiszadeh, M R J Green, T H Scott-Taylor |
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Rok vydání: | 2006 |
Předmět: |
Adult
Lipopolysaccharides Male T-Lymphocytes CD14 CD40 Ligand Immunology Antigen presentation Major histocompatibility complex Phagocytosis Clinical Studies medicine Humans Immunology and Allergy Antigen-presenting cell Cells Cultured Aged CD86 Microscopy Confocal CD40 biology Common variable immunodeficiency Cell Differentiation Dendritic Cells HLA-DR Antigens Dendritic cell Middle Aged Flow Cytometry medicine.disease Common Variable Immunodeficiency Case-Control Studies biology.protein Female Biomarkers |
Zdroj: | Clinical and Experimental Immunology. 145:420-427 |
ISSN: | 1365-2249 0009-9104 |
Popis: | Summary Monocyte-derived dendritic cells (MdDCs) from many patients with common variable immunodeficiency (CVID) have been shown recently to have reduced expression of surface molecules associated with maturity. Using flow cytometry and confocal microscopy, we now show that this is due to a partial failure to fix Class II DR molecules on the surface during procedures that induce full maturation in vitro in cells from normal subjects. Major histocompatibility complex (MHC) class I, CD86 and CD83 expression were expressed normally, but CD40 was reduced. These abnormalities are unlikely to be due to prior in vivo exposure of monocytes to lipopolysaccharide (LPS), as addition of LPS to monocytes from normal subjects in vitro caused a different pattern of changes. CVID MdDCs retained Class II DR in the cytoplasm during maturation, showed increased internalization of cross-linked Class II DR surface molecules and were unable to polarize DR within a lipid raft at contact sites with autologous lymphocytes. These cells retained some features of monocytes, such as the ability to phagocytose large numbers of fixed yeast and fluorescent carboxylated microspheres and expression of surface CD14. These abnormalities, if reflected in vivo, could compromise antigen presentation and may be a fundamental defect in the mechanism of the antibody deficiency in a substantial subset of CVID patients. |
Databáze: | OpenAIRE |
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