Rafting with the IL-12 receptor

Rafting with the IL-12 receptor.

In this issue of Blood, Kondadasula and colleagues provide important clues for understanding successful cancer immunotherapy by demonstrating an intriguing mechanism through which CD16 synergizes with IL-12 to induce interferon-gamma (IFN-gamma) production by NK cells.

Up-Regulation of the IL-12 Receptor

Analysis of the multiple interactions between IL-12 and the high affinity IL-12 receptor complex.

IL-12 is a heterodimeric cytokine, composed of a p40 and a p35 subunit, that exerts its biological effects by binding to specific cell surface receptors. Two IL-12R proteins, designated human IL-12 (huIL-12) receptor beta1 (huIL-12Rbeta1) and huIL-12Rbeta2, have been previously identified. These IL-12R individually bind huIL-12 with low affinity and in combination bind huIL-12 with high affinit...

Structure of Il-12 and Its Receptor

Interleukin-12 (IL-12) is a heterodimeric cytokine produced primarily by antigen-presenting cells (monocytes, macrophages, dendritic cells, and B cells). Its production is stimulated by bacteria, bacterial products, and intracellular parasites and enhanced by priming with granulocytemacrophage colony-stimulating factor (CM-CSF) and interferon-y (IFN-’y) or inhibited by IL-b. The major biologica...

Cholera Toxin Suppresses Interleukin (IL)-12 Production and IL-12 Receptor β1 and β2 Chain Expression

Cholera toxin (CT) is a potent mucosal vaccine adjuvant, which has been shown to induce T helper cell type 2 (Th2) responses in systemic and mucosal tissues. We report that CT inhibits the production of interleukin (IL)-12, a major Th2 counterregulatory cytokine. IL-12 p70 production by stimulated human monocytes was inhibited by CT in a dose-dependent manner. This suppression occurred at the l...