Accumulation of NFAT mediates IL-2 expression in memory, but not naïve, CD4+ T cells.

In contrast to naïve CD4+ T cells, memory CD4+ T cells rapidly express high levels of effector cytokines in response to antigen stimulation. The molecular mechanism for this specific behavior is not well understood. The nuclear factor of activated T cells (NFAT) family of transcription factors plays an important role in the transcription of many cytokine genes.

p38 mitogen-activated protein kinase mediates the Fas-induced mitochondrial death pathway in CD8+ T cells.

The p38 mitogen-activated protein kinase (MAPK) signaling pathway can be activated by a variety of stress stimuli such as UV radiation and osmotic stress. The regulation and role of this pathway in death receptor-induced apoptosis remain unclear and may depend on the specific death receptor and cell type. Here we show that binding of Fas ligand to Fas activates p38 MAPK in CD8+ T cells and that activation of this pathway is required for Fas-mediated CD8+ T-cell death.

Regulation of p38 MAP kinase in CD4+ lymphocytes by infliximab therapy in patients with rheumatoid arthritis.

Tumor necrosis factor alpha (TNFalpha) plays a key role in the pathogenesis of rheumatoid arthritis (RA) and most patients treated with anti-TNFalpha agents show significant improvement in both signs and symptoms. While TNFalpha inhibitors rapidly reduce joint inflammation, the mechanisms by which these agents exert their long-term effects remain unclear. The p38 MAP kinase pathway is one of the signaling pathways triggered by TNFalpha and pharmacological inhibitors of this kinase are being developed for use in RA.

Inhibition of NFAT specifically in T cells prevents allergic pulmonary inflammation.

NFAT is a family of transcription factors important in the regulation of cytokine genes and is widely expressed in different lymphoid and nonlymphoid tissues. Consequently, the role of NFAT in CD4+ T cells during an in vivo immune response is not completely clear. In this study, we use transgenic mice expressing a dominant negative NFAT mutant exclusively in T cells to address the role of NFAT in T cells during a Th2 immune response in a model of allergic airway inflammation.

c-Jun NH(2)-terminal kinase (JNK)1 and JNK2 have distinct roles in CD8(+) T cell activation.

The c-Jun NH(2)-terminal kinase (JNK) signaling pathway is induced by cytokines and stress stimuli and is implicated in cell death and differentiation, but the specific function of this pathway depends on the cell type. Here we examined the role of JNK1 and JNK2 in CD8(+) T cells. Unlike CD4(+) T cells, the absence of JNK2 causes increased interleukin (IL)-2 production and proliferation of CD8(+) T cells.

Granulocyte macrophage-colony stimulating factor (GM-CSF) recruits immune cells to the pancreas and delays STZ-induced diabetes.

Granulocyte macrophage-colony stimulating factor (GM-CSF) is one of the most widely used growth factors for enhancing immune responses and is known to recruit and activate antigen-presenting cells (APCs). This study hypothesized that overexpression of this cytokine within the pancreatic beta-cells would recruit, expand, and activate APCs. The question was whether this would lead to tolerance or autoimmunity to pancreatic antigens.