Protective reconstitution of the SCID mouse against reactivation of toxoplasmic encephalitis

Abstract

A SCID mouse model of toxoplasmic encephalitis (TE) is described. Immunologic reconstitution using splenocytes from Toxoplasma gondii-immune allogeneic or nonimmune syngeneic donors was not successful in preventing reactivation of TE in chronically infected SCID mice. Splenocytes from immune syngeneic donors successfully prevented reactivation. Flow cytometry of spleens of transplanted mice demonstrated only transient reconstitution with allogeneic cells, but syngeneic lymphocytes exhibited prolonged engraftment. Reconstitution with syngeneic cells allowed enhanced production of T. gondii-specific antibody. In vitro depletion of CD4+ and CD8+ lymphocytes from BALB/c splenocytes before transplantation into infected SCID mice resulted in survival inferior to that of fully reconstituted SCID mice. Depletion of CD4+ or CD8+ cells before transplantation did not result in mortality, but transfer of CD(4+)-depleted splenocytes resulted in histologic evidence of reactivation of TE, whereas transfer of CD(8+)-depleted cells did not. This model could be used for study of the pathogenesis of TE and applied to the evaluation of therapies for TE in immunocompromised hosts.