CD8+ cell depletion accelerates HIV-1 immunopathology in humanized mice.
Stable engraftment of human lymphoid tissue in NOD/scid-IL-2Rgammacnull 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.
Gorantla
Santhi
S
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Makarov
Edward
E
Finke-Dwyer
Jennifer
J
Gebhart
Catherine L
CL
Domm
William
W
Dewhurst
Stephen
S
Gendelman
Howard E
HE
Poluektova
Larisa Y
LY
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D036101:Cord Blood Stem Cell Transplantation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D015375:Receptors, Interleukin-2 / Q000172:deficiency / Q000235:genetics
D015375:Receptors, Interleukin-2