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- W1969217131 abstract "Abstract: Decreased production of T helper type 1 (Th1) cytokines, such as interferon-γ (IFN-γ) or interleukin-2 (IL-2), is a hallmark of atopic diseases. While accessory signals from antigen-presenting cells may be missing, T cells themselves may be suppressed in their ability to produce substantial amounts of Th1 cytokines. We show, in this study, that T cell receptor (TCR)-activated T cells from atopic dermatitis (AD) patients proliferate less than control T cells and produce lower amounts of IFN-γ and IL-2, but comparable amounts of IL-4. Because mice lacking the nuclear factor kappa B (NF-κB) transcription factors – p65 or c-Rel – show reduced Th1, but undisturbed Th2 responses, we investigated the role of c-Rel and p65 for Th1 cytokine production in T cells from healthy and severe AD patients. TCR-activated primary T cells from healthy donors treated with c-Rel antisense oligonucleotides produced lower levels of IL-2 and IFN-γ and proliferated less efficiently than the corresponding control T cells. Moreover, transfection of primary T cells with c-Rel or p65 enhanced proliferation and production of IL-2 and IFN-γ. Nuclear extracts of activated primary T cells from AD donors bound weakly to NF-κB-specific oligonucleotides, compared to extracts from healthy control T cells. Western blotting studies revealed that nuclear, but not cytosolic, extracts from T cells of AD patients lacked significant amounts of c-Rel and p65. T cell clones derived from AD patients failed to sufficiently translocate c-Rel and p65 into the nucleus following activation. Thus, impaired nuclear translocation of c-Rel and p65 may determine an impaired Th1 cytokine response in AD." @default.
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- W1969217131 date "2005-01-01" @default.
- W1969217131 modified "2023-09-26" @default.
- W1969217131 title "Deficient translocation of c-Rel is associated with impaired Th1 cytokine production in T cells from atopic dermatitis patients" @default.
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- W1969217131 doi "https://doi.org/10.1111/j.0906-6705.2005.00241.x" @default.
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