Article: article from journal or magazin.
Characterization of hu-PBL-SCID mice with high human immunoglobulin serum levels and graft-versus-host disease
American Journal of Pathology
Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. --- Old month value: Nov
A chimeric model consisting of severe combined immune deficiency (SCID) mice populated with human peripheral blood leukocytes (PBL) has recently been described (bu-PBL-SCID mice). These reports indicated a limited reconstruction of the transferred human immune system and functionality of the human graft. Herein we described modifications of the PBL transfer method that minimize transfer time and cellular manipulations, leading to a more effective population of SCID mouse recipients. Severe combined immune deficiency mice given 15 x 10(6) PBL had human IgG serum levels reaching 2 to 5 g/l, and all mice had detectable human anti-tetanus toxoid antibody levels when they received cells from donors with such levels. These transfers were associated also with clinical and histologic evidence of graft-versus-host disease, suggesting responsiveness of the human graft in the recipients. When Epstein-Barr virus seropositive (EBV+) donors were used, the chimeric mice also showed a high incidence of fatal lymphoproliferative disease 1 to 3 months after transfer of 15 x 10(6) PBL. The high level of immunoglobulin synthesis and immunoresponsiveness of the human cells with this transfer procedure may expand the use of these chimeric mice for the manipulations of human immune cells in vivo.
Animals Antibodies, Viral/analysis B-Lymphocytes/immunology/pathology Blotting, Southern Cryopreservation DNA, Viral/analysis/genetics Electrophoresis/methods Graft vs Host Disease/*blood/immunology/pathology Herpesvirus 4, Human/genetics/immunology Humans Immunoglobulin G/*analysis/immunology Immunoglobulin M/analysis Immunohistochemistry In Situ Hybridization Incidence Leukocytes/*pathology/physiology Lymphoproliferative Disorders/epidemiology/etiology Mice Mice, SCID/*blood Polymerase Chain Reaction T-Lymphocytes/immunology/pathology Tetanus Toxoid/immunology
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