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

被引：65

作者：

Gorantla, Santhi ^{[1
]}

Makarov, Edward ^{[1
]}

Finke-Dwyer, Jennifer ^{[1
]}

Gebhart, Catherine L. ^{[2
]}

Domm, William ^{[3
]}

Dewhurst, Stephen ^{[3
]}

Gendelman, Howard E. ^{[1
,2
]}

Poluektova, Larisa Y. ^{[1
]}

机构：

[1] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE 68198 USA

[2] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE 68198 USA

[3] Univ Rochester, Sch Med & Dent, Dept Microbiol & Immunol, Rochester, NY 14642 USA

来源：

JOURNAL OF IMMUNOLOGY | 2010年 / 184卷 / 12期

基金：

美国国家卫生研究院;

关键词：

HUMAN-IMMUNODEFICIENCY-VIRUS; ADAPTIVE IMMUNE-RESPONSES; CYTOTOXIC T-LYMPHOCYTES; PBL-SCID MICE; DENDRITIC CELLS; MEDIATE PROTECTION; MOUSE MODEL; INFECTION; VIREMIA; BLOOD;

D O I：

10.4049/jimmunol.1000438

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：7082 / 7091

页数：10

共 59 条

[1] Use of a novel chimeric mouse model with a functionally active human immune system to study human immunodeficiency virus type 1 infection [J].

An, Dong Sung ;

Poon, Betty ;

Tsong Fang, Raphael Ho ;

Weijer, Kees ;

Biom, Bianca ;

Spits, Hergen ;

Chen, Irvin S. Y. ;

Uittenbogaart, Christel H. .

CLINICAL AND VACCINE IMMUNOLOGY, 2007, 14 (04) :391-396

[2] HIV-specific CD8+ T cells produce antiviral cytokines but are impaired in cytolytic function [J].

Appay, V ;

Nixon, DF ;

Donahoe, SM ;

Gillespie, GMA ;

Dong, T ;

King, A ;

Ogg, GS ;

Spiegel, HML ;

Conlon, C ;

Spina, CA ;

Havlir, DV ;

Richman, DD ;

Waters, A ;

Easterbrook, P ;

McMichael, AJ ;

Rowland-Jones, SL .

JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (01) :63-75

[3] Disseminated and sustained HIV infection in CD34+ cord blood cell-transplanted Rag2-/-γc-/- mice [J].

Baenziger, Stefan ;

Tussiwand, Roxane ;

Schlaepfer, Erika ;

Mazzucchelli, Luca ;

Heikenwalder, Mathias ;

Kurrer, Michael O. ;

Behnke, Silvia ;

Frey, Joachim ;

Oxenius, Annette ;

Joller, Helen ;

Aguzzi, Adriano ;

Manz, Markus G. ;

Speck, Roberto F. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (43) :15951-15956

[4] Depletion of CD8+ cells in sooty mangabey monkeys naturally infected with simian immunodeficiency virus reveals limited role for immune control of virus replication in a natural host species [J].

Barry, Ashley P. ;

Silvestri, Guido ;

Safrit, Jeffrey T. ;

Sumpter, Beth ;

Kozyr, Natalia ;

McClure, Harold M. ;

Staprans, Silvija I. ;

Feinberg, Mark B. .

JOURNAL OF IMMUNOLOGY, 2007, 178 (12) :8002-8012

[5] Mucosal transmission of R5 and X4 tropic HIV-1 via vaginal and rectal routes in humanized Rag-/- γc-/- (RAG-hu) mice [J].

Berges, Bradford K. ;

Akkina, Sarah R. ;

Folkvord, Joy M. ;

Connick, Elizabeth ;

Akkina, Ramesh .

VIROLOGY, 2008, 373 (02) :342-351

[6] Analysis of total human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T-cell responses:: Relationship to viral load in untreated HIV infection [J].

Betts, MR ;

Ambrozak, DR ;

Douek, DC ;

Bonhoeffer, S ;

Brenchley, JM ;

Casazza, JP ;

Koup, RA ;

Picker, LJ .

JOURNAL OF VIROLOGY, 2001, 75 (24) :11983-11991

[7] Why T cells of thymic versus extrathymic origin are functionally different [J].

Blais, Marie-Eve ;

Brochu, Sylvie ;

Giroux, Martin ;

Belanger, Marie-Pier ;

Dulude, Gael ;

Sekaly, Rafick-Pierre ;

Perreault, Claude .

JOURNAL OF IMMUNOLOGY, 2008, 180 (04) :2299-2312

[8] Presence of HIV-1 gag-specific IFN-γ+IL-2+ and CD28+IL-2+ CD4 T cell responses is associated with nonprogression in HIV-1 infection [J].

Boaz, MJ ;

Waters, A ;

Murad, S ;

Easterbrook, PJ ;

Vyakarnam, A .

JOURNAL OF IMMUNOLOGY, 2002, 169 (11) :6376-6385

[9] Induction of Robust Cellular and Humoral Virus-Specific Adaptive Immune Responses in Human Immunodeficiency Virus-Infected Humanized BLT Mice [J].

Brainard, Diana M. ;

Seung, Edward ;

Frahm, Nicole ;

Cariappa, Annaiah ;

Bailey, Charles C. ;

Hart, William K. ;

Shin, Hae-Sook ;

Brooks, Sarah F. ;

Knight, Heather L. ;

Eichbaum, Quentin ;

Yang, Yong-Guang ;

Sykes, Megan ;

Walker, Bruce D. ;

Freeman, Gordon J. ;

Pillai, Shiv ;

Westmoreland, Susan V. ;

Brander, Christian ;

Luster, Andrew D. ;

Tager, Andrew M. .

JOURNAL OF VIROLOGY, 2009, 83 (14) :7305-7321

[10] Antigen-specific T cell responses in human peripheral blood leucocyte (hu-PBL)-mouse chimera conditioned with radiation and an antibody directed against the mouse IL-2 receptor β-chain [J].

Cao, T ;

Leroux-Roels, G .

CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2000, 122 (01) :117-123

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