BLT-humanized C57BL/6 Rag2−/−γc−/−CD47−/− mice are resistant to GVHD and develop B- and T-cell immunity to HIV infection
| العنوان: | BLT-humanized C57BL/6 Rag2−/−γc−/−CD47−/− mice are resistant to GVHD and develop B- and T-cell immunity to HIV infection |
|---|---|
| المؤلفون: | Todd M. Allen, Ronald J. Messer, Charles Chan, Kerry J. Lavender, Irving L. Weissman, Kim J. Hasenkrug, Dana P. Scott, Wendy W. Pang, Karin E. Peterson, Amanda K. Duley, Timothy Dudek, Brent Race, Katie Phillips, Ulf Dittmer |
| المصدر: | Blood. 122:4013-4020 |
| بيانات النشر: | American Society of Hematology, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | CD4-Positive T-Lymphocytes, Lymphoid Tissue, animal diseases, medicine.medical_treatment, Xenotransplantation, Immunology, Plenary Paper, Medizin, Graft vs Host Disease, chemical and pharmacologic phenomena, HIV Infections, Hematopoietic stem cell transplantation, Biology, Biochemistry, Mice, Immune system, immune system diseases, Immunity, medicine, Animals, Humans, Mesenteric lymph nodes, Mice, Knockout, B-Lymphocytes, Immunity, Cellular, Hematopoietic Stem Cell Transplantation, hemic and immune systems, Cell Biology, Hematology, Transplantation, Disease Models, Animal, surgical procedures, operative, medicine.anatomical_structure, Lymphatic system, HIV-1, Heterografts, Bone marrow |
| الوصف: | The use of C57BL/6 Rag2(-/-)γc(-/-) mice as recipients for xenotransplantation with human immune systems (humanization) has been problematic because C57BL/6 SIRPα does not recognize human CD47, and such recognition is required to suppress macrophage-mediated phagocytosis of transplanted human hematopoietic stem cells (HSCs). We show that genetic inactivation of CD47 on the C57BL/6 Rag2(-/-)γc(-/-) background negates the requirement for CD47-signal recognition protein α (SIRPα) signaling and induces tolerance to transplanted human HSCs. These triple-knockout, bone marrow, liver, thymus (TKO-BLT) humanized mice develop organized lymphoid tissues including mesenteric lymph nodes, splenic follicles and gut-associated lymphoid tissue that demonstrate high levels of multilineage hematopoiesis. Importantly, these mice have an intact complement system and showed no signs of graft-versus-host disease (GVHD) out to 29 weeks after transplantation. Sustained, high-level HIV-1 infection was observed via either intrarectal or intraperitoneal inoculation. TKO-BLT mice exhibited hallmarks of human HIV infection including CD4(+) T-cell depletion, immune activation, and development of HIV-specific B- and T-cell responses. The lack of GVHD makes the TKO-BLT mouse a significantly improved model for long-term studies of pathogenesis, immune responses, therapeutics, and vaccines to human pathogens. |
| تدمد: | 1528-0020 0006-4971 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::df0f96012d5432c9d1efec4d1af158b3 https://doi.org/10.1182/blood-2013-06-506949 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....df0f96012d5432c9d1efec4d1af158b3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
|---|