CD8+ Cell Depletion Accelerates HIV-1 Immunopathology in Humanized Mice

Stable engraftment of human lymphoid tissue in NOD/scid-IL-2Rgc 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. The Journal of Immunology, 2010, 184: 7082-7091.