Human peripheral blood lymphocyte severe combined immunodeficiency (hu-PBLSCID) models of toxoplasmosis

Toxoplasmosis is a potentially fatal opportunistic infection of immunocompr omised hosts. Improved animal models of toxoplasmosis are needed to more ne arly approximate conditions that occur in immunocompromised humans. The dev elopment of models of toxoplasmosis using human peripheral blood lymphocyte s (hu-PBL) transplanted into severe combined immunodeficiency (SCID) mice i s described here. Transplantation of hu-PBL into SCID mice without prior co nditioning of the mice resulted in detectable differences in quantitative h istological scores of brain inflammation due to Toxoplasma gondii infection , but did not alter mortality when compared to SCID mouse controls. The lac k of detectable differences in survival were due to inadequate engraftment of hu-PBL, as assessed by flow cytometry. Unconditioned hu-PBL SCID mice ha d low titre T. gondii- specific antibody detectable after infection. When p retransplantation conditioning with irradiation and antiasialo GM 1 (n-gluc olyl neuraminic acid) antibody was used, prolonged hu-PBL engraftment was o bserved in SCID mice, which was associated with worsened histopathology and usually impaired survival when compared with SCID mouse controls. When pre transplantation conditioning with irradiation, antiasialo GM antibody and p olyethylene glycol-conjugated IL-2 was used, prolonged hu-PBL engraftment w as also documented, but this did not affect survival from T. gondii infecti on when compared with similarly conditioned SCID mouse controls. The latter conditioning protocol resulted in hu-PBL SCID mice producing high titre T. gondii-specific antibody after infection. Conditioned hu-PBL SCID mice had evidence of increased T. gondii-induced inflammatory scores when compared with conditioned SCID mice. These models show promise for the study of the pathogenesis of toxoplasmosis and conditioned hu-PBL SCID mice may have app lications for the evaluation of novel therapies for toxoplasmosis in immuno compromised humans.