ABSTRACT
BACKGROUND: X-linked agammaglobulinaemia (XLA) is a genetic disorder affecting B cell maturation, which is characterised by a low number of B cells, agammaglobulinaemia and increased susceptibility to a variety of bacterial infections. This study was performed to assess T cell subpopulations in a group of children with XLA in association with chronic respiratory disease (CRD). METHODS: Numbers of T cell subpopulations (CD3+, CD4+, CD8+, CD3+DR+, naïve, memory, recent thymic emigrants (RTE), regulatory T cells, follicular T helpers) were measured by eight-colour flow cytometry in 22 XLA patients and 50 controls. BAFF level was measured by ELISA. RESULTS: XLA patients with CRD had a significantly lower percentage of RTE numbers and Tregs, while significantly higher absolute counts of lymphocytes, CD3+, CD8+, CD3+DR+ and CD4+CD45RO+ T cells were detected as compared with healthy controls. In patients with XLA without CRD, the number of follicular T helper cells was altered significantly (percentage and absolute), as compared with healthy controls. Additionally, they had significantly higher counts (percentage and absolute) of CD4+CD45RA+ cells and lower percentage of CD4+CD45RO+ cells in comparison with healthy controls. CONCLUSIONS: Our study affords new information concerning CRD and T cell subsets that differentiate or are maintained in the absence of B cells in children with XLA. T cell's homeostasis depends on the presence of chronic respiratory disease that may be caused by the delay in diagnosis.
Subject(s)
Agammaglobulinemia/immunology , B-Cell Activating Factor/metabolism , Bronchitis/immunology , Genetic Diseases, X-Linked/immunology , Sinusitis/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory/immunology , Thymocytes/immunology , Adolescent , Agammaglobulinemia/complications , Bronchitis/complications , Cell Separation , Child , Child, Preschool , Chronic Disease , Female , Flow Cytometry , Genetic Diseases, X-Linked/complications , Humans , Immunologic Memory , Immunophenotyping , Male , Sinusitis/complicationsABSTRACT
Production of citokines of tumor-necrosis factor (TNF)-alpha and interferon (IFN)-alpha by peripheral blood mononuclear cells (PBMC) from healthy men and from patients with common variable immunodeficiency (CVID) after stimulation with zymosan, lypopolysaccharides, flagellin and CpG, which are ligands of TLR 2/6, TLR 4, TLR 5, TLR 9 respectively, was studied in vitro. In healthy men production of TNF-alpha varied between individuals, whereas synthesis of IFN-alpha was similar. Spontaneous production of TNF-alpha by PBMC in patients with CVID was increased and accompanied by decrease in TNF-alpha production stimulated by each analyzed ligands except CpG. Observed changes in TLR-dependent TNF-alpha production can play important role in pathogenesis of CVID.
Subject(s)
Common Variable Immunodeficiency/immunology , Cytokines/biosynthesis , Immunocompetence/immunology , Toll-Like Receptors/immunology , Adolescent , Adult , Cells, Cultured , Child , Female , Humans , Interferon-alpha/biosynthesis , Leukocytes, Mononuclear/immunology , Ligands , Male , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
The production of TNF-alpha and IFN-alpha cytokines by peripheral blood mononuclears in response to stimulation by TLR2/6, TLR4, TLR5, TLR9 ligands (zymosan, LPS, flagellin, and CpG-oligodeoxynucleotide, respectively) was studied in donors and patients with common variable immunodeficiency. Individual characteristics of TNF-alpha production by mononuclears were revealed in donors. Reduced stimulated production of TNF-alpha in response to stimulation with TLR4 and TLR5 ligands in vitro was detected in patients with common variable immunodeficiency.
Subject(s)
Blood Donors , Common Variable Immunodeficiency/physiopathology , Interferon-alpha/biosynthesis , Toll-Like Receptors/physiology , Tumor Necrosis Factor-alpha/biosynthesis , Adolescent , Adult , Child , Common Variable Immunodeficiency/blood , Female , Flagellin/pharmacology , Humans , Leukocytes, Mononuclear , Lipopolysaccharides/pharmacology , Male , Oligodeoxyribonucleotides/pharmacology , Poly I-C/pharmacology , Toll-Like Receptors/drug effects , Zymosan/pharmacologyABSTRACT
The capacity of leukocytes from children with primary immunodeficiency to produce alpha- and gamma-interferons in vitro was studied. Interferon response of leukocytes in most of the patients examined was found to be practically unchanged. The immunostimulating therapy in some cases exerted a regulating effect on leukocyte capacity for interferon production. It is assumed that the interferon-producing function of T lymphocytes may be preserved in patients suffering from primary immunodeficiency.
