Host Defense Mechanisms Against Murine Cytomegalovirus Infection Induced by Poly l:C in Severe Combined Immune Deficient (SCID) Mice

Abstract

The role of host defense mechanism against murine cytomegalovirus (MCMV) infection in mice with severe combined immunodeficiency (SCID) was investigated using polyinosinic:polycytidylic acid (poly I:C) as a nonspecific stimulator of the immune system. When administered ip at doses of 3.7 or 15 mg/kg 18 hr prior to infection of SCID mice with 10(3) or 10(4) plaque-forming units of MCMV, poly I:C significantly increased the animals' life span. Poly I:C enhanced, in a dose-dependent manner (0.01-1 mg/kg), the peritoneal natural killer (NK)-cell activity and macrophage activity of SCID mice. When SCID mice were pretreated with anti-asialo GM1 antibody (against NK cells) or anti-Mac1 antibody (against macrophages), poly I:C failed to stimulate the activity of NK cells and macrophages. Intraperitoneal administration of poly I:C also induced both early (2 hr) and late (18 hr) type interferon (IFN) in the peritoneal fluid and blood. The IFN-inducing activity of polyl:C was not affected by pretreatment of the mice with anti-asialo GM1 or anti-Mac1 antibody. Poly I:C also caused a significant but less pronounced increase in the life span of MCMV-infected SCID mice in which the NK cells or macrophages had been depleted by treatment with anti-asialo GM1 or anti-Mac1 antibody, respectively. These results suggest that poly I:C-induced interferon as well as activation of NK cell and macrophages contribute to the host defense mechanism against MCMV infection in SCID mice.

Immunisation of Balb/c mice with severely attenuated murine cytomegalovirus mutants induces protective cellular and humoral immunity

“…In SCID mice inoculated intraperitoneally with tcK181 viral replication was initially controlled, presumably by natural killer (NK) cells [Ikeda et al, 1994], but then proceeded rapidly to cause severe disease. In animals inoculated with tsm5 or tsm30, viral replication could also be detected but with considerably delayed kinetics.…”

Human breast cancer cell line xenografts as models of breast cancer — The immunobiologies of recipient mice and the characteristics of several tumorigenic cell lines

“…However, in common with all immunedeficient models, there is individual variation, and some mice may produce detectable levels of two or more IgG isotypes and/or IgM [65]. Macrophages, NK cells [72][73][74][75], and LAK precursor cells [50] are essentially normal in scid mice. However, the mucosal mast cells appear deficient, perhaps due to a lack of specific lymphokines required for their development from progenitors [76].…”