PloS one, 2017-06, Vol.12 (6), p.e0179239-e0179239
2017
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Details
- Autor(en) / Beteiligte
- Titel
- NOG-hIL-4-Tg, a new humanized mouse model for producing tumor antigen-specific IgG antibody by peptide vaccination
- Ist Teil von
- PloS one, 2017-06, Vol.12 (6), p.e0179239-e0179239
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Immunodeficient mice transplanted with human peripheral blood mononuclear cells (PBMCs) are promising tools to evaluate human immune responses to vaccines. However, these mice usually develop severe graft-versus-host disease (GVHD), which makes estimation of antigen-specific IgG production after antigen immunization difficult. To evaluate antigen-specific IgG responses in PBMC-transplanted immunodeficient mice, we developed a novel NOD/Shi-scid-IL2rγnull (NOG) mouse strain that systemically expresses the human IL-4 gene (NOG-hIL-4-Tg). After human PBMC transplantation, GVHD symptoms were significantly suppressed in NOG-hIL-4-Tg compared to conventional NOG mice. In kinetic analyses of human leukocytes, long-term engraftment of human T cells has been observed in peripheral blood of NOG-hIL-4-Tg, followed by dominant CD4+ T rather than CD8+ T cell proliferation. Furthermore, these CD4+ T cells shifted to type 2 helper (Th2) cells, resulting in long-term suppression of GVHD. Most of the human B cells detected in the transplanted mice had a plasmablast phenotype. Vaccination with HER2 multiple antigen peptide (CH401MAP) or keyhole limpet hemocyanin (KLH) successfully induced antigen-specific IgG production in PBMC-transplanted NOG-hIL-4-Tg. The HLA haplotype of donor PBMCs might not be relevant to the antibody secretion ability after immunization. These results suggest that the human PBMC-transplanted NOG-hIL-4-Tg mouse is an effective tool to evaluate the production of antigen-specific IgG antibodies.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0179239Titel-ID: cdi_plos_journals_1910318207
- Format
- –
- Schlagworte
- Analysis, Animals, Antibodies, Antibodies, Neoplasm - genetics, Antibodies, Neoplasm - immunology, Antibody Formation, Antigens, B-Lymphocytes - immunology, B-Lymphocytes - transplantation, Biology and Life Sciences, Blood, Bone marrow, Carrier Proteins - genetics, Carrier Proteins - immunology, CD4 antigen, CD8 antigen, CD8-Positive T-Lymphocytes - immunology, CD8-Positive T-Lymphocytes - transplantation, Cell proliferation, Comparative analysis, ErbB-2 protein, Genetic aspects, Graft vs. host disease, Graft-versus-host reaction, Grafting, Health aspects, Helper cells, Hematology, Heterografts, Histocompatibility antigen HLA, Human performance, Humans, IgG antibody, Immune response, Immunization, Immunodeficiency, Immunoglobulin G, Immunoglobulin G - genetics, Immunoglobulin G - immunology, Interleukin 2 receptors, Interleukin 4, Interleukin-4 - genetics, Interleukin-4 - immunology, Laboratory animals, Leukocytes, Leukocytes (mononuclear), Life sciences, Lymphocytes, Lymphocytes B, Lymphocytes T, Medicine, Medicine and Health Sciences, Mice, Mice, SCID, Mice, Transgenic, Peptides, Peptides - immunology, Peptides - pharmacology, Peripheral blood mononuclear cells, Receptor, ErbB-2 - immunology, Receptor, ErbB-2 - pharmacology, Research and Analysis Methods, Rodents, Studies, Surgery, Th2 Cells - immunology, Th2 Cells - transplantation, Transplantation, Vaccines