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Biomedical subjects

S Raga

Publications and source records attributed to S Raga.

4 recordsLinked to original sources

Elevated serum interleukin (IL)-12p40 levels in common variable immunodeficiency disease and decreased peripheral blood dendritic cells: analysis of IL-12p40 and interferon-gamma gene.

Common variable immunodeficiency disease (CVID) is a heterogeneous syndrome characterized by low immunoglobulin serum levels and recurrent bacterial infections. Several studies suggest that CVID patients have a polarized immune response towards a T helper type 1 phenotype (TH1). However, the factors causing the TH1 polarization remain to be determined in this disease. In the present study, serum interleukin (IL)-12, interferon (IFN)-gamma levels and the IL-12p40 and IFN-gamma gene were studied in CVID patients. Furthermore, we evaluate dendritic cells (DCs) compartment, myeloid dendritic cells (mDCs) and plasmocytoid dendritic cells (pDCs), which help to differentiate naive T cells preferentially into TH1 and TH2, respectively. The serum IL-12p40 subunit levels were increased significantly in CVID patients compared to healthy controls. We examined whether these elevated serum IL-12p40 levels are associated with IFN-gamma or IL-12p40 gene polymorphisms, or with new mutations in the IL-12p40 promoter gene. In our hands, no new mutations were found and gene polymorphisms frequencies in CVID patients were similar to the control population. In conclusion, the elevated serum levels of IL-12p40 found in our CVID patients were not related to these genetic variations. The DC compartment analysis did not show an imbalance between pDCs and mDCs, but revealed the presence of low numbers and percentage of both DC populations in CVID.

Blood Cell Count↗

CD95 expression and function on lymphocyte subpopulations in common variable immunodeficiency (CVID); related to increased apoptosis.

Apoptosis is now recognized as a central process of development and disease, and it has been proposed as one of the mechanisms that may account for the lymphopenia seen in some diseases. In this study we measured spontaneous apoptosis and CD95 expression on different cell subpopulations from CVID patients, using flow cytometric techniques. We divided our patients into two groups according to their CD4+ and CD4+CD45RA+ cell counts. Our results clearly show increased spontaneous apoptosis and CD95 expression on the CD4+ and CD4+CD45RA+ subsets from lymphopenic CVID patients compared with normal subjects and disease controls. Interestingly, our lymphopenic CVID patients presented a profound reduction in absolute counts, mainly affecting the CD4+CD45RA+ subpopulation. We also found a statistically significant direct correlation between absolute numbers of CD4+CD45RA+ T cells and spontaneous apoptosis on the same subset in CVID patients, but attempts to induce CD95-mediated apoptosis were unsuccessful despite increased CD95 expression on CD4+ T cells. These findings suggest that apoptosis could be one of the mechanisms implicated in the significant lymphopenia present in these patients.

Agammaglobulinemia↗

Small cytoplasmic antigens from Pseudomonas aeruginosa stimulate gammadelta T lymphocytes.

Gammadelta T lymphocytes respond to different bacterial antigens and transformed cells. The antigenic molecules responsible for this activity have been studied extensively in antigenic preparations from Mycobacterium. We describe here the in vitro effect of Pseudomonas aeruginosa on gammadelta T lymphocytes and the properties of the implicated compounds. We found a preferential gammadelta T-cell expansion when we used heat-treated P. aeruginosa preparations and a dose-dependent inhibition of proliferation of peripheral blood mononuclear cells (PBMC) when non-heat-treated antigens were studied. This expansion corresponded to a Vgamma9-positive subpopulation. In contrast to alphabeta T lymphocytes, the highest stimulatory activity was restricted to very small cytosolic compounds. This activity was protease resistant and phosphatase sensitive and always dependent on interleukin (IL)-2 or alphabeta T-cell activation. We concluded that the antigenic molecules from P. aeruginosa that activated gammadelta T lymphocytes were small, non-peptidic, phosphorylated compounds, similar to those previously described from Mycobacterium.

Adult↗