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

• Published in: The Journal of immunology (1950) Vol. 154; no. 1; pp. 180 - 191
• Main Authors: Shultz, LD, Schweitzer, PA, Christianson, SW, Gott, B, Schweitzer, IB, Tennent, B, McKenna, S, Mobraaten, L, Rajan, TV, Greiner, DL
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.01.1995
• Subjects: Agammaglobulinemia - genetics; Agammaglobulinemia - immunology; Age Factors; Animals; Complement System Proteins - analysis; Crosses, Genetic; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Female; Humans; Immunity, Cellular; Immunity, Innate; Immunologic Deficiency Syndromes - genetics; Immunologic Deficiency Syndromes - immunology; Immunophenotyping; Interleukin-1 - secretion; Killer Cells, Natural - immunology; Leukocyte Count; Lipopolysaccharides - pharmacology; Longevity; Lymphoid Tissue - immunology; Lymphoid Tissue - pathology; Lymphoma - genetics; Lymphoma - virology; Macrophage Activation - drug effects; Macrophages - immunology; Macrophages - pathology; Male; Mice; Mice, Inbred NOD - genetics; Mice, Inbred NOD - immunology; Mice, Mutant Strains - genetics; Mice, Mutant Strains - immunology; Mice, SCID - genetics; Mice, SCID - immunology; Poly I-C - pharmacology; Severe Combined Immunodeficiency - genetics; Skin Transplantation - immunology; T-Lymphocytes - transplantation; Thymus Neoplasms - genetics; Thymus Neoplasms - virology; Transplantation, Heterologous
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.154.1.180

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.