Rapid evolution of HIV-1 to functional CD8⁺ T cell responses in humanized BLT mice.
Rapid evolution of HIV-1 to functional CD8⁺ T cell responses in humanized BLT mice.
复制标题
HIV-1对人源化BLT小鼠中功能性CD8⁺T细胞反应的快速演变。
DOI：
10.1126/scitranslmed.3003984
复制
发表时间：
2012-07-18
影响因子：
17.1
通讯作者：
Allen TM
中科院分区：
文献类型：
--
作者：
Dudek TE;No DC;Seung E;Vrbanac VD;Fadda L;Bhoumik P;Boutwell CL;Power KA;Gladden AD;Battis L;Mellors EF;Tivey TR;Gao X;Altfeld M;Luster AD;Tager AM;Allen TM
通过将人免疫细胞和组织移植到免疫缺陷小鼠中，包括最近描述的人源化BLT小鼠模型，在开发新型小鼠/人嵌合体方面取得了重要进展，这为促进人体免疫应答的体内研究带来了巨大希望。然而，关于人源化小鼠的细胞免疫应答在多大程度上准确反映了在人类中观察到的细胞免疫应答的数据很少。作为模型病原体，我们用HIV-1感染人源化BLT小鼠，并在感染的急性期表征HIV-1特异性免疫应答和病毒进化。这些小鼠中的HIV-1特异性CD 8 + T细胞应答在其特异性、动力学和免疫优势方面与人类中的那些非常相似。病毒序列进化也揭示了从这些反应中快速和高度可重复的逃逸，反映了在自然HIV-1感染期间观察到的对宿主免疫压力的适应。此外，表达保护性HLA-B*57等位基因的小鼠表现出对病毒复制的增强控制，并将相同的CD 8 + T细胞应答限制在HIV-1 Gag的保守区域，这些保守区域对其在人类中控制HIV-1至关重要。这些数据表明，人源化BLT小鼠模型似乎准确地再现了人类病原体特异性细胞免疫和控制模型人类病原体所需的基本免疫机制，这些方面对于人类病原体的小动物模型的实用性至关重要。
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.
登录
查看更多内容
DOI：
10.1086/655653
发表时间：
2010-10-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Boutwell CL;Rolland MM;Herbeck JT;Mullins JI;Allen TM
通讯作者：
Allen TM
DOI：
10.1073/pnas.071548198
发表时间：
2001-04-24
影响因子：
11.1
作者：
Flores-Villanueva, PO;Yunis, EJ;Goldfeld, AE
通讯作者：
Goldfeld, AE
影响因子：
5.4
作者：
Brockman, Mark A.;Schneidewind, Arne;Allen, Todd M.
通讯作者：
Allen, Todd M.
影响因子：
5.4
作者：
Allen, TM;Altfeld, M;Walker, BD
通讯作者：
Walker, BD
影响因子：
--
作者：
An, Dong Sung;Poon, Betty;Uittenbogaart, Christel H.
通讯作者：
Uittenbogaart, Christel H.