Thymic dendritic cells express inducible nitric oxide synthase and generate nitric oxide in response to self- and alloantigens

Thymocytes maturing in the thymus undergo clonal deletion/apoptosis when th ey encounter self- or allo-Ags presented by dendritic cells (DCs). How this occurs is a matter of debate, but NO may play a role given its ability of inducing apoptosis of these cells. APC (a mixed population of macrophages ( M phi) and DCs) from rat thymus expressed high levels of inducible NO synth ase (MOS) and produced large amounts of NO in basal conditions whereas iNOS expression and NO production were very low in thymocytes. Analysis by FAGS and by double labeling of cytocentrifuged preparations showed that DCs and M phi both express MOS within APC, Analysis of a purified preparation of D Cs confirmed that these cells express high levels of iNOS and produce large amounts of NO in basal conditions. The capacity of DCs to generate NO was enhanced by exposure to rat albumin, a self-protein, and required a fully e xpressed process of Ag internalization, processing, and presentation. Pepti des derived from portions of class II MHC molecules up-regulate iNOS expres sion and NO production by DCs as well, both in self and allogeneic combinat ions, suggesting a role of NO in both self and acquired tolerance. We also found that NO induced apoptosis of rat double-positive thymocytes, the effe ct being more evident in anti-CD3-stinulated cells. Altogether, the present findings might suggest that DC-derived NO is at least one of the soluble f actors regulating events, in the thymus, that follow recognition of self- a nd allo-Ags.