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Altered dendritic cell function in response to sera of common variable immunodeficiency patients
M Nourizadeh1, A Aghamohammadi, S M Moazzeni
1Immunology, Asthma and Allergy Research Institute, Medical Sciences University of Tehran, Tehran, Iran. mnourizadeh@razi.tums.ac.ir
Insights
Common variable immunodeficiency (CVID) patient sera impair dendritic cell function, suggesting soluble factors influence immune responses. Further research is needed to identify these specific factors.
Area of Science:
- Immunology
- Cell Biology
Background:
- Common variable immunodeficiency (CVID) is marked by hypogammaglobulinemia and T cell dysfunction.
- The role of microenvironmental factors, particularly serum components, in dendritic cell (DC) perturbations in CVID is not fully understood.
Purpose of the Study:
- To investigate the impact of CVID patient sera on the differentiation and function of monocyte-derived dendritic cells (MDCs).
- To assess whether serum-derived factors in CVID influence MDC maturation, allostimulatory capacity, and cytokine production.
Main Methods:
- MDCs were generated from monocytes cultured with GM-CSF, IL-4, and either CVID patient sera (n=10) or healthy control sera (n=8).
- MDCs were matured and analyzed for immunophenotype, mixed lymphocyte reaction (MLR) capacity, and cytokine production upon stimulation.
Main Results:
- CVID sera treatment resulted in reduced HLA-DR surface expression on mature MDCs.
- Activated MDCs cultured with CVID sera produced higher levels of IL-18.
- MDCs derived from CVID sera exhibited diminished allostimulatory capacity in MLR assays.
Conclusions:
- Soluble factors in CVID patient sera appear to modulate MDC function, potentially shifting immune responses towards cellular immunity.
- These findings highlight the influence of the microenvironment on DC function in CVID and warrant further investigation to identify specific causative factors.
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.
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