title: CD8+ cell depletion accelerates HIV-1 immunopathology in humanized mice.
abstract: 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.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Santhi
authors.initials: S
authors.lastname: Gorantla
authors.forename: Edward
authors.initials: E
authors.lastname: Makarov
authors.forename: Jennifer
authors.initials: J
authors.lastname: Finke-Dwyer
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Gebhart
authors.forename: William
authors.initials: W
authors.lastname: Domm
authors.forename: Stephen
authors.initials: S
authors.lastname: Dewhurst
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.forename: Larisa Y
authors.initials: LY
authors.lastname: Poluektova
mesh_terms: 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
chemical_list: D015375:Receptors, Interleukin-2