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

OBJECTIVE

CVID is characterized by hypogammaglobulinemia and T cell disorder in most cases. Dendritic cells might be severely perturbed in differentiation and maturation but it is not clear whether this perturbation is intrinsic or because of alterations in microenvironmental factors. We evaluated the effects of CVID patient's sera as a source of microenvironmental factors on monocyte-derived DCs (MDCs).

METHODS

Monocyte derived DCs (MDCs) were generated in the presence of GM-CSF, IL-4 and 10% concentration of CVID (n = 10) and healthy control (n = 8) serum samples. MDCs were matured with monocyte conditioned medium and TNF-alpha. Mature MDCs were used for: (i) immunophenotyping, (ii) MLR, (iii) co-culture with allogeneic lymphocytes for cytokine production assays and (iv) DC-cytokine production assays after stimulation with CD40L.

RESULTS

Treatment of MDCs with sera derived from CVID patients as compared to control sera: (i) causes lower surface expression of HLA-DR after maturation, (ii) leads to production of higher amounts IL-18 by activated MDCs and, (iii) results in lower allostimulatory capacity of MDCs in MLR assays.

CONCLUSIONS

Our findings argue for constitutive presence/absence of soluble factors e. g. cytokines in CVID patients' sera steering the immune response toward the cellular rather than the humoral arm. Our observations deserve further studies to identify these factors.