ANTIBODY-RESPONSES TO TOXOPLASMA-GONDII ANTIGEN IN HUMAN PERIPHERAL-BLOOD LYMPHOCYTE-RECONSTITUTED SEVERE-COMBINED IMMUNODEFICIENT MICE REPRODUCE THE IMMUNOLOGICAL STATUS OF THE LYMPHOCYTE DONOR
W. Walker et al., ANTIBODY-RESPONSES TO TOXOPLASMA-GONDII ANTIGEN IN HUMAN PERIPHERAL-BLOOD LYMPHOCYTE-RECONSTITUTED SEVERE-COMBINED IMMUNODEFICIENT MICE REPRODUCE THE IMMUNOLOGICAL STATUS OF THE LYMPHOCYTE DONOR, European Journal of Immunology, 25(5), 1995, pp. 1426-1430
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.