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© 1994 Oxford University Press

research-article

Development of Human Lymphocyte-Engrafted SCID Mice as a Model for Immunotoxicity Assessment

PAMELA L. POLLOCK, DORI R. GERMOLEC, CHRISTINE E. COMMENT, GARY J. ROSENTHAL and MICHAEL I. LUSTER

Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences P.O Box 12233. Research Triangle Park, North Carolina 27709

Received December 16, 1992; accepted July 29, 1993

Mice with the severe combined immunodeficient (SCID) and triple-deficient (bg/nu/;xid) 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, bg/;nu/;xid 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 engraftments than mice from the bg/;nu/;xid or C3H-SCID strains. Using optimal conditions, mo-SPL-SCID and hu-PBL-SCID mice were engrafted and administered either 2,3,7,8-tetrachloro- dibenzo-p-dioxin or cyclosporin A (Cys A) and periodically bled to measure tetanus-specific antibody and class-specific immuno globulin concentrations. Comparison of the chemical-related changes in immunoglobulin and tetanus antibody concentrations revealed some similarities between control mice and mo SPL-SCID or hu-PBL-SCID mice, particularly with Cys A groups. However, under the various conditions examined, hu PBL-SCID mice demonstrated considerable variability in their ability to provide consistent reconstitution, thus, limiting the ability to determine whether human cells are more or less suscep tible than mouse cells to the test agents. Provided that this sys tem can be refined to provide consistent reconstitution, hu PBL-SCID mice may be a promising in vivo model for assessment of potential immunotoxic agents.


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