0000000000294238

AUTHOR

Maria Dittmayer

Targeting of the transcription factor STAT4 by antisense phosphorothioate oligonucleotides suppresses collagen-induced arthritis

Abstract The transcription factor STAT4 mediates signals of various proinflammatory cytokines, such as IL-12, IL-15, and IL-23, that initiate and stabilize Th1 cytokine production. Although Th1 cytokine production has been suggested to play a major pathogenic role in rheumatoid arthritis, the role of STAT4 in this disease is poorly understood. In this study, we demonstrate a key functional role of STAT4 in murine collagen-induced arthritis (CIA). In initial studies we found that STAT4 expression is strongly induced in CD4+ T cells and to a lesser extent in CD11b+ APCs during CIA. To analyze the role of STAT4 for arthritis manifestation, we next investigated the outcome of interfering with S…

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Inhibition of anti-GD3-ganglioside antibody-induced proliferation of human CD8+ T cells by CD16+ natural killer cells

The ganglioside GD3 has been described as a membrane component of human T cells which is involved in T cell growth. In the present study the activating function of GD3 for human CD4+ and CD8+ T cells was analyzed by five different monoclonal antibodies (mAb) directed against the GD3 molecule. Three mAb U5, Z21 and R24 induced strong proliferation of peripheral blood mononuclear cells and purified CD8+ and CD4+ T cells of normal donors containing less than 5% CD16+ natural killer (NK) cells. In contrast to CD4+ T cells, CD8+ T cells proliferated only weakly in the presence of 15% CD16+ NK cells. The proliferative response of purified CD4+ and CD8+ T cells (< 5% NK cells) correlated with the …

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