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• W1976165637 abstract "ABSTRACT The generation of humanized BLT mice by the cotransplantation of human fetal thymus and liver tissues and CD34 + fetal liver cells into nonobese diabetic/severe combined immunodeficiency mice allows for the long-term reconstitution of a functional human immune system, with human T cells, B cells, dendritic cells, and monocytes/macrophages repopulating mouse tissues. Here, we show that humanized BLT mice sustained high-level disseminated human immunodeficiency virus (HIV) infection, resulting in CD4 + T-cell depletion and generalized immune activation. Following infection, HIV-specific humoral responses were present in all mice by 3 months, and HIV-specific CD4 + and CD8 + T-cell responses were detected in the majority of mice tested after 9 weeks of infection. Despite robust HIV-specific responses, however, viral loads remained elevated in infected BLT mice, raising the possibility that these responses are dysfunctional. The increased T-cell expression of the negative costimulator PD-1 recently has been postulated to contribute to T-cell dysfunction in chronic HIV infection. As seen in human infection, both CD4 + and CD8 + T cells demonstrated increased PD-1 expression in HIV-infected BLT mice, and PD-1 levels in these cells correlated positively with viral load and inversely with CD4 + cell levels. The ability of humanized BLT mice to generate both cellular and humoral immune responses to HIV will allow the further investigation of human HIV-specific immune responses in vivo and suggests that these mice are able to provide a platform to assess candidate HIV vaccines and other immunotherapeutic strategies." @default.
• W1976165637 created "2016-06-24" @default.
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• W1976165637 date "2009-07-15" @default.
• W1976165637 modified "2023-10-16" @default.
• W1976165637 title "Induction of Robust Cellular and Humoral Virus-Specific Adaptive Immune Responses in Human Immunodeficiency Virus-Infected Humanized BLT Mice" @default.
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• W1976165637 doi "https://doi.org/10.1128/jvi.02207-08" @default.
• W1976165637 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2704767" @default.
• W1976165637 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19420076" @default.
• W1976165637 hasPublicationYear "2009" @default.
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