Cell-mediated and not humoral immune responseis responsible for partial protection against toxoplasmosis in SCID mice reconstituted with human PBMC

RESUMEN

El objetivo de este estudio fue profundizar en el conocimiento de la respuesta inmunologica especifica contra Toxoplasma en humanos. Usamos ratones SCID reconstituidos con PBMC de donantes sanos con y (..)(CNS) (AU)

ABSTRACT

The aim of this study was to further our understanding of the human Toxoplasma-specific immune response. We used severe combined immune deficiency (SCID) mice that had been reconstituted with peripheral blood mononuclear cells (PBMC) from healthy donors with and without serum Toxoplasma antigens(PBMC Toxo+ and PBMC Toxo-, respectively) and subsequently infected with parasite cysts. The specific lymphocyte proliferation rate (LPR) was higher for PBMC from Toxoplasma-immune donors and these PBMC secreted more Th1 cytokines than those obtained from Toxoplasma-non-immune donors. The engraftmentof human parasite-immune cells significantly increased the survival rate following infection compared to in unreconstituted animals,where as the engraftment of human non-parasite-immune cells did not alter the survival rate. Specific human anti-Toxoplasma antibodies were found in both groups of humanised animals, suggesting that the humoral immune response does not play a major role in this protection. Ten days after infection, cytometry revealed that there were more human CD45+ cells in the spleen and peritoneum of mice from the PBMC Toxo+ group than from the PBMC Toxo- group. Furthermore, plasma levels of nitric oxide(NO) peaked at an early stage of infection in resistant animals.Finally, no human CD4 mRNA or IFN-¦Ã mRNA was found in the brain during infection. All together, our results suggest that the human cell-mediated immune response provides partial protection against toxoplasmic encephalitis (TE) in this model. However,the effector mechanisms involved may be located outside of the central nervous system (CNS) (AU)