INTACT IMMUNE DEFENSES ARE REQUIRED FOR MICE TO RESIST THE TS-4 VACCINE STRAIN OF TOXOPLASMA-GONDII

The ts-4 strain of Toxoplasma gondii is a temperature-sensitive mutant that fails to grow at 40 degrees C in vitro. Unlike mildly virulent c yst-forming strains, which can cause fatal chronic infections in certa in mouse strains, ts-4 has been widely used to vaccinate mice against virulent T. gondii and is a valuable tool with which to investigate me chanisms of acquired resistance to this parasite. In this report, the basis for the avirulence of ts-4 is analyzed. It is shown that ts-4 is able to persist long-term in vivo in mildly immunocompromised mice, w hich rules out an intrinsic growth defect as a reason for avirulence. ts-4 does not induce body temperatures in mice as high as that needed to kill it in vitro. Moreover, the mild fevers elicited in resistant B 6 mice are also seen in susceptible C57BL/6 scid/scid mice. However, t s-4 elicits strong preimmune defenses, dependent on gamma interferon, which are needed by mice to survive acute infection. Furthermore, CD4( +) and CD8(+) T-cell-dependent acquired immunity is essential for long -term survival of ts-4-infected mice.