GSBS Student Publications

Title

Enhanced human CD4+ T cell engraftment in beta2-microglobulin-deficient NOD-scid mice

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Medicine, Diabetes Division; Department of Pediatrics

Date

4-15-1997

Document Type

Article

Medical Subject Headings

Animals; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes; Crosses, Genetic; *Graft Survival; Humans; Mice; Mice, Inbred NOD; Mice, SCID; beta 2-Microglobulin

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: J Immunol. 1997 Apr 15;158(8):3578-86.

Related Resources

Link to article in PubMed

Journal Title

Journal of immunology (Baltimore, Md. : 1950)

PubMed ID

9103418