Engrafted Human T and B Lymphocytes Form Mixed Follicles in Lymphoid Organs of Human/Mouse and Human/Rat Radiation Chimera1

Burakova, Tanya; Marcus, Hadar; Canaan, Allon; Dekel, Benjamin; Shezen, Elias; David, Michel; Lubin, Ido; Segal, Harry L.; Reisner, Yaīr

doi:10.1097/00007890-199704270-00018

Cited by 17 publications

(11 citation statements)

References 25 publications

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“…Meaningfully, the human T lymphocytes, recovered from Trimera mice within the first month posttransplantation, retain their proliferative capabilities and can mount primary anti‐HIV‐1 cellular immune responses, such as IFN‐γ secretion after their in vitro exposure to an HIV‐1 specific immunogen. The relatively rapid induction of humoral and cellular immune responses may be partially explained by the xenoactivation of the engrafted human cells and by the close proximity between T and B cells in the normal microenvironment of the mouse lymphoid tissues (27).…”

Section: Discussionmentioning

confidence: 99%

“…Most importantly, we have demonstrated that the human engrafted cells can elicit primary and secondary anti‐HIV‐1 humoral and cellular immune responses. It has already been demonstrated that the engrafted human cells, which are engrafted in significant numbers and are found in different internal organs for at least 2 months (20, 21, 27), are in a nonanergized functional status, can form mixed lymphoid follicles similar to germinal centers (27), and can mount primary humoral (26) and cellular (25) human immune responses. The capacity of the engrafted human T and B cells to be in close proximity to each other in the normal microenvironment of the mouse lymphoid tissues (27) is probably crucial for the generation of the human primary and secondary Ab response, here manifested by the initial production of anti‐HIV‐1 IgM isotype Abs followed by production of anti‐HIV‐1 IgG isotype Abs.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to the previous hu‐PBL‐SCID models (15, 23, 24), human PBMC in the Trimera mice do not become anergic and are capable of mounting primary and secondary cellular and humoral specific immune responses (21, 25, 26). In distinction to hu‐PBL‐SCID mice, the tempo of engraftment and the appearance of human T and B cells subpopulations are greatly enhanced in different internal organs as early as 24 h after transplantation (20, 21, 27). The Trimera mice have been successfully used for studying human infections, such as hepatitis C (HCV) (28), hepatitis B (HBV) (29), and influenza (30), and for evaluation of influenza and hepatitis B vaccines (30, 31).…”

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confidence: 99%

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A novel small animal model for HIV‐1 infection

Ayash-Rashkovsky¹,

Bentwich²,

Arditti

et al. 2005

FASEB j.

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Lethally irradiated normal BALB/c mice, reconstituted with murine SCID bone marrow and engrafted with human PBMC (Trimera mice), were used to establish a novel murine model for HIV‐1 infection. The Trimera mice were successfully infected with different clades and primary isolates of T‐ and M‐tropic HIV‐1, with the infection persisting in the animals for 4–6 wk. Rapid loss of the human CD4+ T cells, decrease in CD4/CD8 ratio, and increased T cell activation accompanied the viral infection. All HIV‐1 infected animals were able to generate both primary and secondary immune responses, including HIV specific human humoral and cellular responses. In addition to testing the efficacy of new antiviral compounds, this new murine HIV‐1 model may be used for studying host‐virus interactions and, most importantly, for screening and developing potential HIV‐1 protective vaccines and adjuvants (Ayash‐Rashkovsky et al., http://www.fasebj.org/cgi/doi/10.1096/fj.04-3185fje; doi:.).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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A novel small animal model for HIV‐1 infection

Ayash-Rashkovsky¹,

Bentwich²,

Arditti

et al. 2005

FASEB j.

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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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“…Since these chimera contain tissues from three different sources (murine recipient, SCID mouse BM donor, human PBMC donor), the mice were termed trimera 17. 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.…”

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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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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Engrafted Human T and B Lymphocytes Form Mixed Follicles in Lymphoid Organs of Human/Mouse and Human/Rat Radiation Chimera1

Cited by 17 publications

References 25 publications

A novel small animal model for HIV‐1 infection

A novel small animal model for HIV‐1 infection

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

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

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