Distribution of parasite stages in tissues of Toxoplasma gondii infected SCID mice and human peripheral blood lymphocyte-transplanted SCID mice.

Abstract

The establishment of Toxoplasma gondii infection in the tissues of SCID mice and SCID mice transplanted with human peripheral blood lymphocytes (PBL) was investigated. The presence of bradyzoites and tachyzoites was analysed in hu-PBL SCID mice using Southern blot of reverse transcriptase-polymerase chain reaction products for the expression of B1, BAG1 and SAG1 of T. gondii. BAG1 was present by week 1 in brain, lung, liver and spleen of some animals; by week 3, BAG1 was present in all animals and in all of these tissues. In contrast, SAG1 was rarely detected until week 2 (mainly in the lung and brain) and by week 3, some animals still did not have detectable SAG1 in brain, lung, liver and spleen. SAG1 expression was increased in the lungs of animals transplanted with human PBL compared to nontransplanted SCID mice. Human PBL engraftment was demonstrated, initially in uninfected mice, by the presence of human CD3+ T cells in the spleen (3.1 x 10(5) positive cells) and peritoneal cavity (3.4 x 10(5) cells) 4 weeks after transplantation. The final outcome of infection was not influenced by the presence of human PBL, with similar mortality in human PBL transplanted and nontransplanted mice. These studies provide a detailed analysis of the kinetics and distribution of both the cyst and tachyzoite stage of T. gondii. This system has been established to allow evaluation of therapies against T. gondii immunodeficient mice in the presence of human immune cells.