NITRIC-OXIDE CAUSES THE MACROSCHIZONTS OF THEILERIA-ANNULATA TO DISAPPEAR AND HOST-CELLS TO BECOME APOPTOTIC

The proliferation of Theileria annulata macroschizont-infected cell li nes in vitro was significantly inhibited by nitric oxide (NO) generate d by S-nitroso-N-acetyl-DL-penicillamine (SNAP). Incubation with SNAP caused the macroschizonts to disappear and host cells to become apopto tic. SNAP-derived NO also significantly inhibited the incorporation of tritiated thymidine by cultures of cells in which the schizonts had b een induced to differentiate into merozoites by maintenance at 41 degr ees C instead of 37 degrees C, the temperature used for culturing macr oschizont-infected cells. These results point to NO as the mediator of macrophage anti-T. annulata activity and provide new evidence that th e protective immune mechanisms which allow cattle to recover from prim ary infection and resist challenge may be attributed principally to th e products of activated macrophages. These findings indicate that effe ctive inactivated vaccines against T. annulata should include antigens able to stimulate the type of CD4(+) T cell response which elicits ma crophage activation and NO synthesis.