Human → mouse radiation chimera do not develop Epstein-Barr virus lymphoma

Marcus, Hadar; Burakova, Tanya; Shezen, Elias; David, Michel; Canaan, Allon; Lubin, Ido; Reisner, Yaīr

doi:10.1016/0165-2478(96)02497-2

Cited by 11 publications

(3 citation statements)

References 16 publications

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“…As shown in Fig. 1, rather weak antigen‐specific Th cell responses were induced by day 10 after vaccination in three out of five mice receiving 10 μg HBcAG 13 ± 19 spot‐forming cells (SFC) / 10 5 ) peritoneal cells], while high T cell frequencies were induced in the mice provided with HBc‐pulsed DC (169 ± 102 SFC / 10 5 peritonel cells). In contrast, the mice receiving 10 μg BB antigen developed high specific Th cell frequencies (188 ± 39 SFC / 10 5 peritoneal cells) and the substitution of BB‐pulsed DC had no additional effect (180 ± 87 SFC / 10 5 peritoneal cells) (Fig.…”

Section: Resultsmentioning

confidence: 92%

“…Due to the existence of preformed murine lymphatic organs, the engraftment of transferred human T and B cells reaches its peak already within the first 3 weeks post‐transplant with formation of lymphoid follicles in peritoneum, lymph nodes and spleen 16, 18. Moreover, high numbers of human lymphocytes can be transplanted into different strains of mice without the complications of GvHD or EBV lymphomas 19. This advantageous kinetic and structural engraftment pattern facilitates the generation of antigen‐specific B and T cell responses by vaccination in vivo 20, 21.…”

Section: Introductionmentioning

confidence: 99%

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Induction of strong hepatitis B virus (HBV) specific T helper cell and cytotoxic T lymphocyte responses by therapeutic vaccination in the trimera mouse model of chronic HBV infection

et al. 2001

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Humanized BALB / c mice (termed trimera mice) conditioned by lethal total body irradiation and bone marrow transplantation from SCID mice have been described to support rapid engraftment of human peripheral blood mononuclear cells (PBMC) and the induction of strong B and T cell responses after immunization in vivo. Moreover, these mice can be infected with the hepatitis B and C viruses (HBV, HCV). The current study employed this model to study therapeutic vaccination approaches against the HBV. Thus, strong primary Th cell responses against the HBV core (HBc) and the Borrelia burgdorferi control antigen were induced by transfer of antigen‐loaded dendritic cells together with autologous PBMC from HBV‐naive donors as well as by vaccination with high doses of antigen or a DNA plasmid encoding for HBcAg. Moreover, primary peptide‐specific CTL responses against the immunodominant epitope HBc18 – 27 were induced by HBc particle or DNA vaccination of chimera engrafted with HBV‐naive PBMC. Finally, strong HBc‐specific Th cell and antibody responses were induced by HBc or DNA vaccination of mice reconstituted with PBMC from a chronic HBV patient. Thus, since HBc represents the immunodominant antigen in self‐limited HBV infection, HBc particles or DNA vectors are good candidates for therapeutic vaccination, that will be further studied in ourmodel and clinical studies.

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Section: Resultsmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Induction of strong hepatitis B virus (HBV) specific T helper cell and cytotoxic T lymphocyte responses by therapeutic vaccination in the trimera mouse model of chronic HBV infection

et al. 2001

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“…It is also known as Trimera or humanized mice. The chimera mice has engrafted with peripheral blood mononuclear cells (PBMCs) in Balb/c mice, which have already lethally irradiated and transplanted by the bone marrow of NOD (knockout mice) mice [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Nanovaccine for immunotherapy and reduced hepatitis-B virus in humanized model

Dewangan

Pandey

Singh

2017

Artificial Cells, Nanomedicine, and Biotechnology

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Chronic Hepatitis B Virus (HBV) infections are severe with weak antiviral immune responses. The lack of an appropriate small animal model for chronic hepatitis, a major hurdle for studying the immunotolerance and immunopathogenesis induced by hepatitis B viral (HBV) infection. In this study, for enhancing the antibody production efficiency the prepared polymeric HBsAg-loaded nanoparticles (nanovaccine) will be tested in immune-deficit mice, which suffer from chronic Hepatitis B virus. Vaccination of Balb/c mice by this prepared nanoparticles that were engrafted with peripheral blood mononuclear cells (PBMCs), which was already lethally irradiated and transplanted by the bone marrow of NOD (knockout mice) mice. In the present study, after the vaccination detected the high frequencies of immunoglobulin G (IgG)-secreting B cells and mitogen-responsive interferon-Y (IFN-Y) secreting T cells in serum, determined by specific ELISA technique. During the entire observation period, unvaccinated animals showed lower concentration of specific IgG secreting B cells and IFN-Y secreting T cells found in comparison to vaccinated mice group. Chronic HBV carrier PBMCs transplanted into the chimera failed to produce antigen and increased the antibodies production due to vaccination. Furthermore, another advantage was that the viral gene expression and viral DNA replication was no longer observed in vaccinated group. This prepared nanovaccine formulations is better for the cure of Hepatitis B viral infection carrier. Therefore, specific memory responses were elicited by vaccination with Hepatitis B virus surface (HBsAg) antigen of chimeric mice transplanted with PBMCs derived from HBV donors.

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Human/BALB radiation chimera engrafted with splenocytes from patients with idiopathic thrombocytopenic purpura produce human platelet antibodies

et al. 1998

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SUMMARYWe have previously shown that lethally irradiated normal strains of mice, radioprotected with severe combined immunodeficient (SCID) bone marrow, can be engrafted with human peripheral blood mononuclear cells (PBMC ). The human/mouse radiation chimera can mount marked humoral and cellular responses to recall antigens, as well as primary responses. In the present study, we adoptively transferred splenocytes from patients with chronic immune thrombocytopenic purpura (ITP) into lethally irradiated BALB/c mice, radioprotected with SCID bone marrow. High titres of total human immunoglobulin appeared as early as 2 weeks post-transplant and declined after 6 weeks, while human anti-human platelet antibodies were detected 2-8 weeks after the transfer of splenocytes. The immunoglobulin G (IgG) fraction contained antibodies against glycoprotein (GP) IIb/IIIa (CD41) or GPIb/IX (CD42). The human platelet antibodies showed a low level of cross-reactivity with mouse platelets, and thrombocytopenia in the animals was not observed. Splenocytes from individual ITP patients differed in their capacity to produce either human platelet antibodies or total human immunoglobulin. Furthermore, antibodies produced in the murine system were not always identical to the original antibodies present in the serum of the patients. The study of the serological aspects of autoantibodies against human platelets in an animal model might be useful for the investigation of potential therapeutics in ITP.

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Human → mouse radiation chimera do not develop Epstein-Barr virus lymphoma

Cited by 11 publications

References 16 publications

Induction of strong hepatitis B virus (HBV) specific T helper cell and cytotoxic T lymphocyte responses by therapeutic vaccination in the trimera mouse model of chronic HBV infection

Induction of strong hepatitis B virus (HBV) specific T helper cell and cytotoxic T lymphocyte responses by therapeutic vaccination in the trimera mouse model of chronic HBV infection

Nanovaccine for immunotherapy and reduced hepatitis-B virus in humanized model

Human/BALB radiation chimera engrafted with splenocytes from patients with idiopathic thrombocytopenic purpura produce human platelet antibodies

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