Title
Enhanced human CD4+ T cell engraftment in beta2-microglobulin-deficient NOD-scid mice
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Medicine, Diabetes Division; Department of Pediatrics
Publication Date
1997-04-15
Document Type
Article
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.
Source
J Immunol. 1997 Apr 15;158(8):3578-86.
Journal/Book/Conference Title
Journal of immunology (Baltimore, Md. : 1950)
Related Resources
PubMed ID
9103418
Repository Citation
Christianson SW, Greiner DL, Hesselton RM, Leif JH, Wagar EJ, Schweitzer IB, Rajan TV, Gott B, Roopenian DC, Shultz LD. (1997). Enhanced human CD4+ T cell engraftment in beta2-microglobulin-deficient NOD-scid mice. GSBS Student Publications. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/221