Rapid Evolution of HIV-1 to Functional CD8 + T Cell Responses in Humanized BLT Mice
| العنوان: | Rapid Evolution of HIV-1 to Functional CD8 + T Cell Responses in Humanized BLT Mice |
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| المؤلفون: | Priyasma Bhoumik, Xiaojiang Gao, Lena Fadda, Laura Battis, Marcus Altfeld, Todd M. Allen, Andrew D. Luster, Trevor Tivey, Vladimir Vrbanac, Karen A. Power, Andrew M. Tager, Edward Seung, Elizabeth F. Mellors, Timothy Dudek, Adrianne D. Gladden, Daniel C. No, Christian L. Boutwell |
| المصدر: | Science Translational Medicine. 4 |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Immunity, Cellular, Cellular immunity, T cell, HIV Infections, Cellular Immunology, General Medicine, Immunodominance, CD8-Positive T-Lymphocytes, Biology, Article, Mice, medicine.anatomical_structure, Immune system, HLA-B Antigens, Immunity, Immunology, HIV-1, medicine, Animals, Humans, Cytotoxic T cell, CD8 |
| الوصف: | Important advancements in the development of novel mouse/human chimeras through the engraftment of human immune cells and tissues into immunodeficient mice, including the recently described humanized BLT mouse model, holds great promise to facilitate the in vivo study of human immune responses. However, little data exists regarding the extent to which cellular immune responses in humanized mice accurately reflect those seen in humans. As a model pathogen we infected humanized BLT mice with HIV-1 and characterized HIV-1-specific immune responses and viral evolution during the acute phase of infection. HIV-1-specific CD8+ T cell responses in these mice were found to closely resemble those in humans in terms of their specificity, kinetics and immunodominance. Viral sequence evolution also revealed rapid and highly reproducible escape from these responses, mirroring the adaptations to host immune pressures observed during natural HIV-1 infection. Moreover, mice expressing the protective HLA-B*57 allele exhibited enhanced control of viral replication, and restricted the same CD8+ T cell responses to conserved regions of HIV-1 Gag that are critical to its control of HIV-1 in humans. These data reveal that the humanized BLT mouse model appears to accurately recapitulate human pathogen-specific cellular immunity and the fundamental immunological mechanisms required to control a model human pathogen, aspects critical to the utility of a small animal model for human pathogens. |
| تدمد: | 1946-6242 1946-6234 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2acd3b54a0e9c48a18a8d87dfbf55c95 https://doi.org/10.1126/scitranslmed.3003984 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2acd3b54a0e9c48a18a8d87dfbf55c95 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19466242 19466234 |
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