Effects of nitric oxide on the induction and differentiation of Th1 cells

We have previously shown that mice lacking inducible NO synthase are marked ly more susceptible to Leishmania major infection but developed a significa ntly enhanced Th1 cell response compared with wild-type mice. Furthermore, at high concentrations, NO inhibited IL-12 synthesis by activated macrophag es, thereby indirectly suppressing the expansion of Th1 cells. We report he re that at low concentrations, NO selectively enhanced the induction of Th1 cells and had no effect on Th2 cells,NO exerted this effect in synergy wit h IL-12 during Th1 cell differentiation and had no effect on fully committe d Th1 cells. NO appears to affect CD4(+) T cells directly and not at the an tigen-presenting cells. These results therefore provide an additional pathw ay by which NO modulates the immune response and contributes to the homeost asis of the immune system.