Faculty Research 1990 - 1999

Title

Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice.

Document Type

Article

Publication Date

1995

Keywords

Age-Factors, Animal, Complement: an, Crosses-Genetic, Diabetes-Mellitus-Insulin-Dependent: ge, im, Female, Human, Immunity-Cellular, Immunity-Natural, Immunologic-Deficiency-Syndromes: ge, im, Immunophenotyping, Interleukin-1: se, Killer-Cells-Natural: im, Leukocyte-Count, Lipopolysaccharides, Longevity, Lymphoid-Tissue: im, pa, Lymphoma: ge, Macrophage-Activation: de, Macrophages: im, pa, Male, Mice, Mice-Inbred-NOD: ge, im, Mice-Mutant-Strains: ge, im, Mice-SCID: ge, im, Poly-I-C, Severe-Combined-Immunodeficiency: ge, Skin-Transplantation: im, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes: tr, Thymus-Neoplasms: ge, Transplantation-Heterologous

JAX Source

J Immunol 1995 Jan 1;154(1):180-91

Grant

AI30389/AI/NIAID, CA20408/CA/NCI, CA34196/CA/NCI

Abstract

The scid mutation was backcrossed ten generations onto the NOD/Lt strain background, resulting in an immunodeficient stock (NOD/LtSz-scid/scid) with multiple defects in adaptive as well as nonadaptive immunologic function. NOD/LtSz-scid/scid mice lack functional lymphoid cells and show little or no serum Ig with age. Although NOD/(Lt-)+/+ mice develop T cell-mediated autoimmune, insulin-dependent diabetes mellitus, NOD/LtSz-scid/scid mice are both insulitis- and diabetes-free throughout life. However, because of a high incidence of thymic lymphomas, the mean lifespan of this congenic stock is only 8.5 mo under specific pathogen-free conditions. After i.v. injection of human CEM T-lymphoblastoid cells, splenic engraftment of these cells was fourfold greater in NOD/LtSz-scid/scid mice than in C.B17/Sz-scid/scid mice. Although C.B-17Sz-scid/scid mice exhibit robust NK cell activity, this activity is markedly reduced in both NOD/(Lt-)+/+ and NOD/LtSz-scid/scid mice. Presence of a functionally less mature macrophage population in NOD/LtSz-scid/scid vs C.B-17Sz-scid/scid mice is indicated by persistence in the former of the NOD/Lt strain-specific defect in LPS-stimulated IL-1 secretion by marrow-derived macrophages. Although C.B-17Sz-scid/scid and C57BL/6Sz-scid/scid mice have elevated serum hemolytic complement activity compared with their respective +/+ controls, both NOD/(LtSz-)+/+ and NOD/LtSz-scid/scid mice lack this activity. Age-dependent increases in serum Ig levels (> 1 micrograms/ml) were observed in only 2 of 30 NOD/LtSz-scid/scid mice vs 21 of 29 C.B-17/Sz-scid/scid animals. The multiple defects in innate and adaptive immunity unique to the NOD/LtSz-scid/scid mouse provide an excellent in vivo environment for reconstitution with human hematopoietic cells.

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