ANTIBODY-RESPONSES TO TOXOPLASMA-GONDII ANTIGEN IN HUMAN PERIPHERAL-BLOOD LYMPHOCYTE-RECONSTITUTED SEVERE-COMBINED IMMUNODEFICIENT MICE REPRODUCE THE IMMUNOLOGICAL STATUS OF THE LYMPHOCYTE DONOR

These studies describe the production of specific antibodies in human peripheral blood lymphocyte-reconstituted severe-combined immunodefici ent (PBL-SCID) mice following vaccination with antigen from the protoz oan parasite Toxoplasma gondii. To determine the effect of previous ex posure of the lymphocyte donor to antigen, human-PBL-SCID animals were created by transferring peripheral blood lymphocytes from either a si ngle T. gondii-seronegative or a single seropositive donor. These reco nstituted animals were subsequently inoculated with T. gondii soluble tachyzoite antigen (STAg) entrapped within non-ionic surfactant vesicl es as an immunological adjuvant. Animals were bled at pre-determined t ime points post-vaccination and the expression of human anti-STAg anti bodies in the plasma determined by enzyme-linked immunosorbent assay. Human antibodies specific for STAg were readily inducible in both grou ps of reconstituted animals, although the pattern of isotype productio n differed markedly between groups. The response in animals reconstitu ted with lymphocytes from the T. gondii-seronegative donor consisted p rimarily of IgM and subsequently of IgG (predominantly IgG1). In anima ls reconstituted with lymphocytes from the seropositive donor, no para site-specific IgM could be demonstrated. The detectable response to ST Ag consisted entirely of human antibodies of the IgG isotype (IgG1), i ndicative of a memory-type response. These results mimicked exactly th e antibody responses that would be expected had the lymphocyte donors been directly challenged with either the antigen or the live infectiou s agent, demonstrating that the immune system within these animals is functional and reproducible with regard to both the primary and second ary responses of the human donors.