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Human immunodeficiency virus infection of xenografted SCID-beige mice
B W McBride1, L M Easterbrook, G H Farrar
1Microbial Antigens Department, CAMR, Salisbury, Wiltshire, United Kingdom.
The application of C.B-17 SCID-Beige mice as an experimental animal system for the acceptance of human leukocyte xenografts, the establishment of functional human immune responses and infection with HIV has been assessed. Reconstitution efficiencies approaching 100% could be obtained by using 2 x 10(7) human peripheral blood lymphocytes (PBLs). Typical levels of human immunoglobulin in mouse blood reached 120 micrograms/ml within 2 weeks of reconstitution rising to a maximum in excess of 3 mg/ml by 5 weeks. Immunohistological examination of lung, spleen, lymph node and thymus tissue, derived from reconstituted mice, with human leukocyte specific monoclonal antibodies revealed the presence of human macrophages (CD68+), T cells (CD43+) and B cells (CD20+). The establishment of a functional immune system was demonstrated by the ability of reconstituted mice to respond to immunisation with KLH. Finally, reconstituted Hu-PBL-SCID-Beige mice were susceptible to infection with HIV-1 by intraperitoneal injection. These results indicate that SCID-Beige mice are a valuable tool for the generation of human/mouse chimeras and for the establishment of an in vivo HIV infection model. The results are compared with other similar model systems and are discussed in the context of animal models of HIV vaccine studies.
The application of C.B-17 SCID-Beige mice as an experimental animal system for the acceptance of human leukocyte xenografts, the establishment of functional human immune responses and infection with HIV has been assessed. Reconstitution efficiencies approaching 100% could be obtained by using 2 x 10(7) human peripheral blood lymphocytes (PBLs). Typical levels of human immunoglobulin in mouse blood reached 120 micrograms/ml within 2 weeks of reconstitution rising to a maximum in excess of 3 mg/ml by 5 weeks. Immunohistological examination of lung, spleen, lymph node and thymus tissue, derived from reconstituted mice, with human leukocyte specific monoclonal antibodies revealed the presence of human macrophages (CD68+), T cells (CD43+) and B cells (CD20+). The establishment of a functional immune system was demonstrated by the ability of reconstituted mice to respond to immunisation with KLH. Finally, reconstituted Hu-PBL-SCID-Beige mice were susceptible to infection with HIV-1 by intraperitoneal injection. These results indicate that SCID-Beige mice are a valuable tool for the generation of human/mouse chimeras and for the establishment of an in vivo HIV infection model. The results are compared with other similar model systems and are discussed in the context of animal models of HIV vaccine studies.