The Scid Mouse Reaction to Human Peripheral Blood Mononuclear Leukocyte Engraftment

Sanit, IT Istituto Superiore di; Santini, Stefano M.; Rizza, Paola; Logozzi, Mariantonia; Sestili, Paola; Gherardi, Giovanni; Lande, Roberto; Lapenta, Caterina; Belardelli, Filippo; Fais, Stefano

doi:10.1097/00007890-199512150-00020

Cited by 3 publications

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“…It has been reported that the presence of human cells in SCID mice induces a wide spectrum of murine cytokines, including IL‐1β, IL‐4, IL‐6, IL‐10, IL‐12, TNF‐α and IFN‐γ (Santini et al . 1995).…”

Section: Discussionmentioning

confidence: 99%

Distribution of parasite stages in tissues of Toxoplasma gondii infected SCID mice and human peripheral blood lymphocyte‐transplanted SCID mice

Meyer

Allan

Beaman

2000

Parasite Immunology

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The establishment of Toxoplasma gondii infection in the tissues of SCID mice and SCID mice transplanted with human peripheral blood lymphocytes (PBL) was investigated. The presence of bradyzoites and tachyzoites was analysed in hu-PBL SCID mice using Southern blot of reverse transcriptase-polymerase chain reaction products for the expression of B1, BAG1 and SAG1 of T. gondii. BAG1 was present by week 1 in brain, lung, liver and spleen of some animals; by week 3, BAG1 was present in all animals and in all of these tissues. In contrast, SAG1 was rarely detected until week 2 (mainly in the lung and brain) and by week 3, some animals still did not have detectable SAG1 in brain, lung, liver and spleen. SAG1 expression was increased in the lungs of animals transplanted with human PBL compared to nontransplanted SCID mice. Human PBL engraftment was demonstrated, initially in uninfected mice, by the presence of human CD3+ T cells in the spleen (3.1 x 10(5) positive cells) and peritoneal cavity (3.4 x 10(5) cells) 4 weeks after transplantation. The final outcome of infection was not influenced by the presence of human PBL, with similar mortality in human PBL transplanted and nontransplanted mice. These studies provide a detailed analysis of the kinetics and distribution of both the cyst and tachyzoite stage of T. gondii. This system has been established to allow evaluation of therapies against T. gondii immunodeficient mice in the presence of human immune cells.

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Section: Discussionmentioning

confidence: 99%

Distribution of parasite stages in tissues of Toxoplasma gondii infected SCID mice and human peripheral blood lymphocyte‐transplanted SCID mice

Meyer

Allan

Beaman

2000

Parasite Immunology

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“…These mice exhibit spontaneous secretion of human immunoglobulin (IgG) and can produce a specific human antibody response when induced with an immunization of tetanus toxoid [ 62 ]. At one day post injection, there is a large neutrophil recruitment and an induced expression of murine cytokine mRNA (IL-1 β, IL-4, IL-6, IL-10, IL-12, TNF-α and IFN-γ) that occurs in the mouse peritoneal cavity [ 99 ]. After the first three weeks of expansion of the PBL in the peritoneal cavity, the human leukocytes, specifically CD4+ or CD8+ SP T cells expressing alpha/beta T-cell receptors, begin to appear in the mouse liver and spleen [ 100 ].…”

Section: Humanized Murine Models Of Hiv-1 Infectionmentioning

confidence: 99%

The utilization of humanized mouse models for the study of human retroviral infections

et al. 2009

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The development of novel techniques and systems to study human infectious diseases in both an in vitro and in vivo settings is always in high demand. Ideally, small animal models are the most efficient method of studying human afflictions. This is especially evident in the study of the human retroviruses, HIV-1 and HTLV-1, in that current simian animal models, though robust, are often expensive and difficult to maintain. Over the past two decades, the construction of humanized animal models through the transplantation and engraftment of human tissues or progenitor cells into immunocompromised mouse strains has allowed for the development of a reconstituted human tissue scaffold in a small animal system. The utilization of small animal models for retroviral studies required expansion of the early CB-17 scid/scid mouse resulting in animals demonstrating improved engraftment efficiency and infectivity. The implantation of uneducated human immune cells and associated tissue provided the basis for the SCID-hu Thy/Liv and hu-PBL-SCID models. Engraftment efficiency of these tissues was further improved through the integration of the nonobese diabetic (NOD) mutation leading to the creation of NODSCID, NOD/Shi-scid IL2rγ -/-, and NOD/SCID β2-microglobulin null animals. Further efforts at minimizing the response of the innate murine immune system produced the Rag2 -/-γ c -/-model which marked an important advancement in the use of human CD34+ hematopoietic stem cells. Together, these animal models have revolutionized the investigation of retroviral infections in vivo.

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Pertussis toxin B-oligomer inhibits HIV infection and replication in hu-PBL-SCID mice

Lapenta

Spada

Santini

et al. 2005

International Immunology

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Bordetella pertussis toxin B-oligomer (PTX-B) has been shown to inhibit HIV infection and replication in vitro. The potential anti-viral effect of PTX-B was tested here in an in vivo surrogate model of HIV infection, i.e. SCID mice reconstituted with human peripheral blood leukocytes (PBL) (hu-PBL-SCID) and infected with a CCR5-dependent (R5) HIV-1 strain. SCID mice inoculated intra-peritoneal (i.p.) with PTX-B and then infected with the R5 strain SF-162 were sacrificed 7 days later and analyzed for human PBL (hu-PBL) lymphoid tissue reconstitution, infection of hu-PBL, plasma viremia and viral rescue from ex vivo-cultivated i.p. hu-PBL. Unlike mice treated with 500 ng per animal of PTX-B showing no evidence of viral inhibition, daily administration of PTX-B (50 ng per mouse) strongly inhibited virus infection and replication, as determined by undetectable viremia, absence of infected hu-PBL and lack of rescue of infectious HIV in most animals. Furthermore, PTX-B injection 2 h before and twice after infection prevented HIV-1 infection and replication in all (10/10) tested animals. Thus, PTX-B potently inhibited virus infection and replication in hu-PBL-SCID mice, supporting the hypothesis that it may represent a new pharmacological agent against HIV-1 infection.

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The Scid Mouse Reaction to Human Peripheral Blood Mononuclear Leukocyte Engraftment

Cited by 3 publications

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Distribution of parasite stages in tissues of Toxoplasma gondii infected SCID mice and human peripheral blood lymphocyte‐transplanted SCID mice

Distribution of parasite stages in tissues of Toxoplasma gondii infected SCID mice and human peripheral blood lymphocyte‐transplanted SCID mice

The utilization of humanized mouse models for the study of human retroviral infections

Pertussis toxin B-oligomer inhibits HIV infection and replication in hu-PBL-SCID mice

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