Antibody isotype responses to Trichuris infection in humanized SCID mice.

Abstract

We have developed a humanized SCID mouse model of trichuriasis involving the injection of peripheral blood lymphocytes (PBLs) from normal healthy donors into C. B. 17 severe combined immunodeficiency (SCID) mice followed by vaccination and infection of these mice with the murine species of Trichuris, Trichuris muris. Optimal results with respect to parasite specific antibody production and peripheral engraftment were achieved by injecting intraperitoneally 2 x 10(7) PBLs which had been incubated overnight on anti-human CD3 coated plates. Mice were immunized three weeks post reconstitution with parasite antigen in Freund's Incomplete Adjuvant and infected two weeks later. At autopsy human T cells could be detected in the spleens of engrafted animals and anti-T. muris antibody detected. The dominant IgG isotype responses were shown to be IgG1 and IgG2, providing a similar IgG isotype profile to that seen in humans infected with T. trichiura in the field. In several cases engrafted animals showed the remarkable ability to expel their parasite load. The model will thus be useful for analysing human immune responses to trichuriasis under highly controlled laboratory conditions impossible to achieve in the field.