Regulation of Lymphocytes by Nitric Oxide

Shortly after the identification of nitric oxide (NO) as a product of macrophages, it was discovered that NO generated by inducible NO synthase (iNOS) inhibits the proliferation of T lymphocytes. Since then, it has become clear that iNOS activity also regulates the development, differentiation, and/or function of various types of T cells and B cells and also affects NK cells. The three key mechanisms underlying the iNOS-dependent immunoregulation are (a) the modulation of signaling processes by NO, (b) the depletion of arginine, and (c) the alteration of accessory cell functions. This chapter highlights important principles of iNOS-dependent immunoregulation of lymphocytes and also reviews more recent evidence for an effect of endothelial or neuronal NO synthase in lymphocytes.