Temperature-Sensitive Mutants of Toxoplasma gondii: Pathogenicity and Persistence in Mice

Abstract

Certain temperature-sensitive mutants of the RH strain of T. gondii and a back mutant, all maintained in human fibroblasts, were studied in mice. Most mutants gave rise to acute, fatal infections and after sulfonamide prophylaxis rarely persisted as chronic infections in mice. The ts-4 strain was nonfatal in doses up to 103-105 tachyzoites, elicited high titers of antibody and did not persist beyond 2 mo. No Toxoplasma cysts were found. There was no evidence that a febrile reaction of the mice was restrictive, because the highest temperatures, 37.9-38.4 C, occurred 3 days after infection; the organisms were recoverable for 16-32 days. Because doses of Toxoplasma, survived by 11 of 12 normal BALB/c mice, and by 1 of 5 thymic transplanted athymic mice, killed 6 of 6 athymic mice, it appears that the limited persistence of ts-4 is related to the immunologic response.