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• W2071709931 abstract "Peripheral blood lymphocytes (PBL) and alloreactive T cell lines of two male infants born to consanguinous parents and presenting with severe combined immunodeficiency (SCID) showed a pronounced deficiency in T cell activation. Although phenotypically normal, the proliferative response of the childrens' T cells was strongly reduced but could be improved by the addition of interleukin-2 (IL-2). Furthermore both childrens'T cells were unable to produce the cytokines IL-2, interferon-γ (IFN-γ), IL-4 and tumor necrosis factor-α (TNF-α). This multiple cytokine production deficiency could not be restored by IL-2 or co-stimulatory signals provided by antigen-presenting cells (APC). Moreover, mRNA for IL-2 and IFN-γ could not be detected. In contrast, expression of the activation-dependent cell surface markers CD25 and CD69 was within normal limits. To determine whether the functional defect of the patients' T cells was due to the absence or abnormal binding of transcription factors involved in cytokine gene expression, electrophoretic mobility shift assays were used to examine the DNA binding of AP-1, Oct, CREB, SP1, NF-ϰB and the nuclear factor of activated T cells (NF-AT) to their respective response elements in the promoter of the IL-2 gene. Whereas AP-1, NF-ϰB, Oct, CREB and SP1 displayed normal binding activities in nuclear extracts, the binding of NF-AT to its IL-2 promoter response element was barely detectable both before and after T cell stimulation. Our results strongly suggest that this NF-AT/DNA binding defect is responsible for the multiple cytokine deficiency and the SCID phenotype observed in the two infant brothers." @default.
• W2071709931 created "2016-06-24" @default.
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• W2071709931 date "1996-09-01" @default.
• W2071709931 modified "2023-10-04" @default.
• W2071709931 title "Severe combined immunodeficiency due to defective binding of the nuclear factor of activated T cells in T lymphocytes of two male siblings" @default.
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• W2071709931 doi "https://doi.org/10.1002/eji.1830260924" @default.
• W2071709931 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/8814256" @default.
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