REGULATION OF THE IMMUNE-RESPONSE BY NITRIC-OXIDE DIFFERENTIALLY PRODUCED BY T-HELPER TYPE-1 AND T-HELPER TYPE-2 CELLS

The balance between T helper type 1 (Th 1) and T helper type 2 (Th 2) cells determines the outcome of many important diseases. Using cloned murine T cell lines, evidence is provided that Th 1, but not Th 2, cel ls can be activated by specific antigens or a T cell mitogen, concanav alin A, to produce large amounts of nitric oxide (NO). Furthermore, NO can inhibit the secretion of interleukin (IL)-2 and interferon-gamma by Th 1 cells but has no effect on IL-4 production by Th 2 cells. Th 1 and Th 2 cells can, thus, be distinguished by their differential prod uction of and susceptibility to NO. NO exerts a self-regulatory effect on Th 1 cells which are implicated in immunopathology.