Development of human lymphocyte-engrafted SCID mice as a model for immunotoxicity assessment

Mice with the severe combined immunodeficient (SCID) and triple-deficient (bglnulxid) mutations lack select populations of functional immune cells. Studies by several laboratories have demonstrated the ability to restore certain missing immune com-ponents in these mice by reconstituting with various lymphoid tissues including peripheral blood lymphocytes (PBL) from mice and humans. Such a model could provide an opportunity to examine human lymphoid cells in an in vivo environment for immunotoxicity assessment. In the present studies, bglnulxid and SCID mice were reconstituted by intraperitoneal or intrave-nous injection with either tetanus-immunized syngeneic mouse splenocytes (mo-SPL) or tetanus-immunized human PBLs (hu-PBL) under various test conditions. Hu-PBL-SCID mice from the C.B-17 strain produced more successful human engraft-ments than mice from the bglnulxid or C3H-SCID strains. Us