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

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53 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7082-7091
Number of pages10
JournalJournal of Immunology
Volume184
Issue number12
DOIs
StatePublished - Jun 15 2010

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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