Enhanced human CD4+ T cell engraftment in beta2-microglobulin-deficient NOD-scid mice.
- Citation data:
Journal of immunology (Baltimore, Md. : 1950), ISSN: 0022-1767, Vol: 158, Issue: 8, Page: 3578-86
- Publication Year:
- Repository URL:
- https://mouseion.jax.org/stfb1990_1999/864; https://escholarship.umassmed.edu/gsbs_sp/221
- Immunology and Microbiology; Animal; Crosses-Genetic; CD4-CD8-Ratio; CD4-Positive-T-Lymphocytes: im; tr; Graft-Survival; Human; Mice; Mice-Inbred-NOD; Mice-SCID; SUPPORT-NON-U-S-GOVT; SUPPORT-U-S-GOVT-P-H-S; Life Sciences; Medicine and Health Sciences; CD4-Positive-T-Lymphocytes: im, tr
Genetic crosses produced NOD/LtSz mice doubly homozygous for the severe combined immunodeficiency (scid) mutation and the beta2m (B2m) null allele. Both NOD/LtSz-scid/scid and NOD/LtSz-scid/scid B2m(null) mice lacked mature lymphocytes and serum Ig. However, homozygosity for the B2m(null) allele also resulted in the absence of MHC class I expression, loss of NK cell activity, accumulation of iron in the liver, and rapid clearance of human IgG1. NOD/LtSz-scid/scid B2m(null) mice supported markedly elevated levels of human T cell engraftment, compared with NOD/LtSz-scid/scid control animals, following injection with human PBMC. The increased engraftment was associated with a major increase in the number of human CD4+ T cells. Following injection with 20 million human PBMC, levels of human CD4+ T cells in the peripheral blood and spleen of NOD/ LtSz-scid/scid B2m(null) mice were 6- to 7-fold higher than those in NOD/LtSz-scid/scid mice and >50-fold higher than those in C.B-17-scid/scid mice. The resulting normalization of CD4+/CD8+ ratios in NOD/LtSz-scid/scid B2m(null) mice is in sharp contrast to that observed in NOD/LtSz-scid/scid mice or in C.B-17-scid/scid mice. Circulating human IgG was cleared 6-fold more rapidly in NOD/LtSz-scid/scid B2m(null) mice than in NOD/LtSz-scid/scid mice. This rapid IgG clearance suggested a failure of the engrafted human lymphoid cells to maintain high circulating levels of human IgG. The higher levels of human CD4+ T cells and the normalization of the CD4:CD8 ratio that are observed in human PBMC-engrafted NOD/LtSz-scid/scid B2m(null) mice suggest that this system may be an excellent model for studies of HIV pathogenesis.