concanavalin-a and Behcet-Syndrome

Inducible costimulator (ICOS) is an important costimulatory molecule involved in T-cell activation. In this study, the role of ICOS in the pathogenesis of uveitis in Behçet's disease (BD) was investigated.. Peripheral blood mononuclear cells (PBMCs) were obtained from BD patients with uveitis in the active or remission phase and in healthy subjects. Total RNA was isolated from PMBCs, and mRNA expression was analyzed on an oligonucleotide microarray. ICOS expression on CD4(+) T cells was determined by flow cytometry, and the functional costimulatory effect of ICOS/B7RP-1 interaction was assessed on stimulation with concanavalin A (conA) or IRBP in the presence or absence of anti-ICOS mAb.. As the result of microarray analysis, ICOS in PBMCs showed the greatest difference in expression in BD patients with uveitis compared with healthy control subjects. ICOS expression on CD4(+) T cells in BD patients with uveitis was significantly higher than that in healthy individuals, both before and after conA stimulation. Among the BD patients, ICOS expression on CD4(+) T cells was significantly higher in those with active uveitis than in those with remitted uveitis. Blockade of ICOS/B7-related protein-1 (B7RP-1) interaction by anti-ICOS mAb significantly decreased IFN-γ, IL-17, and TNF-α production by PBMCs when stimulated with conA or IRBP in BD with active uveitis.. High ICOS expression in BD patients with uveitis contributed to the upregulation of IFN-γ, IL-17, and TNF-α production, suggesting that abnormal ICOS costimulation may play an immunopathologic role in the pathogenesis of uveitis in BD.

Topics: Adult; Antibodies, Blocking; Antigens, Differentiation, T-Lymphocyte; B7-1 Antigen; Behcet Syndrome; Biomarkers; CD4-Positive T-Lymphocytes; Concanavalin A; Cytokines; Eye Proteins; Female; Flow Cytometry; Gene Expression Profiling; Gene Expression Regulation; Humans; Inducible T-Cell Co-Stimulator Ligand; Inducible T-Cell Co-Stimulator Protein; Lymphocyte Activation; Male; Middle Aged; Oligonucleotide Array Sequence Analysis; Retinol-Binding Proteins; RNA, Messenger; Th1 Cells; Uveitis

To investigate the relationship between the production of Th1/Th2 cytokines and cell kinetics, cell division and proliferation in patients with Behçet's disease (BD).. Peripheral venous blood was drawn from patients with BD (n = 24; 10 patients with active and 14 patients with inactive BD) and normal subjects (n = 22). Peripheral blood mononuclear cells were separated immediately and were cultured with concanavalin A (Con A) followed by phorbol 12-myristate 13-acetate and ionomycin (PMA+Ion). Intracellular cytokine production of interferon-gamma (IFN-gamma) (Th1) and IL-4 (Th2) in CD4(+) T cells was determined by flow cytometry. Furthermore, CD4(+) T cells labelled with CFSE [5 (and 6) carboxyfluorescein diacretate, succinimidyl ester] were stimulated and the cells were analysed for entry into the cytokine production effector pathway during cell division in active BD and normal subjects.. In active BD, enhanced entry into the Th1 response effector pathway of CD4(+) T cells was observed after stimulation with Con A followed by PMA+Ion. Analysis of CD4(+) T cells at an identical cell division number in response to Con A followed by PMA+Ion revealed that IFN-gamma-producing cells were increased in active BD patients compared with normal subjects. These results suggest that the Th1 response of dividing CD4(+) T cells is predominantly operating in active BD. Dividing CD4(+) T cells stimulated with Con A followed by PMA+Ion showed a phenotype of activated effector memory T cells (CD45RA(low), CD45RO(+), CD69(high)).. Cell kinetics play a crucial role in Th1 cell differentiation and pathophysiology in BD.

Topics: Acute Disease; Adult; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Behcet Syndrome; Case-Control Studies; CD4-Positive T-Lymphocytes; Cell Differentiation; Cell Division; Cells, Cultured; Concanavalin A; Female; Humans; Interferon-gamma; Interleukin-4; Lectins, C-Type; Leukocyte Common Antigens; Lymphocyte Activation; Male; Middle Aged; Tetradecanoylphorbol Acetate; Th1 Cells

We investigated serum levels of interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and tumor necrosis factor alpha (TNF alpha) from patients with systemic lupus erythematosus (SLE) and its various clinical manifestations of disease and from patients with rheumatoid arthritis (RA) and other rheumatic diseases. The serum levels of IL-6 and IFN-gamma were highly elevated from patients with SLE associated with lymphadenopathy (LN) or nephrotic syndrome (NS). On the contrary, the serum levels of TNF alpha were elevated from most patients with SLE associated with thrombocytopenia (TP). However, serum levels of TNF alpha were in the normal range from patients with SLE associated with NS, LN, or central nervous system disease. Of interest, patients with SLE associated with humoral immunodeficiency disorder, hypogammaglobulinemia, had highly elevated levels of serum IL-6. The concanavalin A-stimulated mononuclear cells (MNC) of patients with SLE associated with TP secreted highly elevated levels of TNF alpha compared to other patient groups. We suggest that abnormal production of various cytokines in SLE is an intrinsic defect of MNC and the immune system that may be the key element for a variety of clinical manifestations of this disease.

Topics: Adolescent; Adult; Arthritis, Rheumatoid; Behcet Syndrome; Concanavalin A; Cytokines; Female; Humans; Interferon-gamma; Interleukin-6; Lupus Erythematosus, Systemic; Lymphadenitis; Male; Middle Aged; Nephrotic Syndrome; Polymyalgia Rheumatica; Rheumatic Diseases; Sjogren's Syndrome; Thrombocytopenia; Tumor Necrosis Factor-alpha

Topics: Behcet Syndrome; Concanavalin A; Humans; Rosette Formation; T-Lymphocytes, Regulatory

Topics: Adult; Behcet Syndrome; Concanavalin A; Female; Humans; Male; Middle Aged; Rosette Formation; T-Lymphocytes; T-Lymphocytes, Regulatory