CD8+ cell depletion accelerates HIV-1 immunopathology in humanized mice

Santhi Gorantla; Edward Makarov; Jennifer Finke-Dwyer; Catherine L Gebhart; William Domm; Stephen Dewhurst; Howard E. Gendelman; Larisa Y. Poluektova

doi:10.4049/jimmunol.1000438

CD8⁺ cell depletion accelerates HIV-1 immunopathology in humanized mice

Santhi Gorantla, Edward Makarov, Jennifer Finke-Dwyer, Catherine L Gebhart, William Domm, Stephen Dewhurst, Howard E. Gendelman, Larisa Y. Poluektova

Research output: Contribution to journal › Article › peer-review

68 Scopus citations

Abstract

Stable engraftment of human lymphoid tissue in NOD/scid-IL- 2Rγ_c^null mice after CD34⁺ hematopoietic stem cell reconstitution permits the evaluation of ongoing HIV-1 infection for weeks to months. We demonstrate that HIV-1-infected rodents develop virus-specific cellular immune responses. CD8⁺ cell depletion, 2 or 5-7 wk after viral infection, resulted in a significant increase of HIV-1 load, robust immune cell activation, and cytopathology in lymphoid tissues but preserved CD4/CD8 double-positive thymic T cell pools. Human CD8⁺ cells reappeared in circulation as early as 2-3 wk. These data support a role of CD8⁺ cells in viral surveillance and the relevance of this humanized mouse model for the studies of HIV-1 pathobiology and virus-specific immunity.

Original language	English (US)
Pages (from-to)	7082-7091
Number of pages	10
Journal	Journal of Immunology
Volume	184
Issue number	12
DOIs	https://doi.org/10.4049/jimmunol.1000438
State	Published - Jun 15 2010

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.4049/jimmunol.1000438

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abstract = "Stable engraftment of human lymphoid tissue in NOD/scid-IL- 2Rγcnull mice after CD34+ hematopoietic stem cell reconstitution permits the evaluation of ongoing HIV-1 infection for weeks to months. We demonstrate that HIV-1-infected rodents develop virus-specific cellular immune responses. CD8+ cell depletion, 2 or 5-7 wk after viral infection, resulted in a significant increase of HIV-1 load, robust immune cell activation, and cytopathology in lymphoid tissues but preserved CD4/CD8 double-positive thymic T cell pools. Human CD8+ cells reappeared in circulation as early as 2-3 wk. These data support a role of CD8+ cells in viral surveillance and the relevance of this humanized mouse model for the studies of HIV-1 pathobiology and virus-specific immunity.",

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AU - Gorantla, Santhi

AU - Makarov, Edward

AU - Finke-Dwyer, Jennifer

AU - Gebhart, Catherine L

AU - Domm, William

AU - Dewhurst, Stephen

AU - Gendelman, Howard E.

AU - Poluektova, Larisa Y.

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AB - Stable engraftment of human lymphoid tissue in NOD/scid-IL- 2Rγcnull mice after CD34+ hematopoietic stem cell reconstitution permits the evaluation of ongoing HIV-1 infection for weeks to months. We demonstrate that HIV-1-infected rodents develop virus-specific cellular immune responses. CD8+ cell depletion, 2 or 5-7 wk after viral infection, resulted in a significant increase of HIV-1 load, robust immune cell activation, and cytopathology in lymphoid tissues but preserved CD4/CD8 double-positive thymic T cell pools. Human CD8+ cells reappeared in circulation as early as 2-3 wk. These data support a role of CD8+ cells in viral surveillance and the relevance of this humanized mouse model for the studies of HIV-1 pathobiology and virus-specific immunity.

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CD8⁺ cell depletion accelerates HIV-1 immunopathology in humanized mice

Abstract

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