Monocyte derived dendritic cell responses in common variable immunodeficiency

Abstract

SUMMARYThe phenotype and function of monocyte derived dendritic cells (MdDC) were investigated in 25 patients with common variable immunodeficiency (CVID) to test for abnormalities that might help explain the failure of antibody production. Using MHC class II DR and CD86 as markers of maturation, DCs from the majority of CVID patients were normal. However 5 patients, the majority of whom had affected family members who had previously been shown to have a susceptibility genetic locus in the MHC region, expressed abnormally low levels of DR on repeated testing, in some cases associated with a reduced capacity to support antigen stimulated T cell proliferation; nevertheless costimulatory molecules for production of IL-13, IL-10 and IFN-g from T cells were intact. In contrast to DCs from healthy donors, DCs from many CVID patients had high spontaneous production of IL-8 and lipopolysaccharide stimulation often caused a reduction in DR expression. Expression of other cytokines (IL-1a, IL-6 and IL-12), either before or after LPS stimulation, was normal. The data suggests there is a fundamental defect in the maturation of MdDCs in a subset of CVID patients that may compromise antigen presentation and subsequent antibody production.

Altered dendritic cell function in response to sera of common variable immunodeficiency patients

“…These results are consistent with the fi ndings of Bayry et al that showed a severely perturbed differentiation and maturation of DCs in CVID patients with decreased expression of CD40, CD80, HLA-DR and other co stimulatory molecules, that resulted in impaired T cell activation and proliferation [17]. Defective antigen presentation of CVID patient's DCs has been also shown by others [32,33]. Scott-Taylor et al, demonstrated a fundamental defect in the maturation of CVID patients MDCs and reduction in HLA-DR expression after LPS stimulation leading to defective antigen presentation and subsequent antibody production [32].…”

Abnormal interleukin-7 function in common variable immunodeficiency

“…3 Thus, the IL-7 dysfunction may also be involved in the defective dendritic cell function recently described in CVID. 19,20 Considering the role of IL-7 in both development and peripheral homeostasis of lymphocytes, 3 it is conceivable that the abnormal IL-7 function as demonstrated in this study may be involved in the skewing of lymphocyte subsets and in the development of an impaired T-and B-cell function in some CVID patients. For personal use only.…”

Immunoglobulin-Dependent Regulation of Dendritic Cells in the Context of Autoimmune Responses

“…The number and function of T cells in XLA patients are generally normal. We showed that DC from CVID patients exhibit defective differentiation [26,27]. However, DC that differentiated in the presence of IVIg presented with an upregulated expression of CD1a and the costimulatory molecules CD80, CD86 and CD40, compared to DC in the presence of autologous plasma alone [28].…”