CD8+ Lymphocytes Are Required for Maintaining Viral Suppression in SIV-Infected Macaques Treated with Short-Term Antiretroviral Therapy

被引:150
作者
Cartwright, Emily K. [1 ,2 ]
Spicer, Lori [1 ,2 ]
Smith, S. Abigail [1 ,2 ]
Lee, David [1 ,2 ]
Fast, Randy [3 ]
Paganini, Sara [1 ,2 ]
Lawson, Benton O. [1 ,2 ]
Nega, Melon [1 ,2 ]
Easley, Kirk [4 ]
Schmitz, Joern E. [5 ,7 ]
Bosinger, Steven E. [1 ,2 ]
Paiardini, Mirko [1 ,2 ]
Chahroudi, Ann [1 ,2 ,6 ]
Vanderford, Thomas H. [1 ,2 ]
Estes, Jacob D. [3 ]
Lifson, Jeffrey D. [3 ]
Derdeyn, Cynthia A. [1 ,2 ]
Silvestri, Guido [1 ,2 ]
机构
[1] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30329 USA
[2] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA
[3] Leidos Biomed Res Inc, Frederick Natl Lab, AIDS & Canc Virus Program, Frederick, MD 21702 USA
[4] Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30329 USA
[5] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA
[6] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA
[7] Fraunhofer Inst Mol Biol & Appl Ecol IME, D-52074 Aachen, Germany
关键词
SIMIAN IMMUNODEFICIENCY VIRUS; T-CELL DEPLETION; MHC CLASS-I; RHESUS MACAQUES; CYCLOSPORINE-A; HIV-INFECTION; MONOCLONAL-ANTIBODY; PLASMA VIREMIA; IMMUNE CONTROL; REPLICATION;
D O I
10.1016/j.immuni.2016.08.018
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Infection with HIV persists despite suppressive anti-retroviral therapy (ART), and treatment interruption results in rapid viral rebound. Antibody-mediated CD8(+) lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows that these cells contribute to viral control in untreated animals. However, the contribution of CD8(+) lymphocytes to maintaining viral suppression under ART remains unknown. Here, we have shown that in SIV-infected RMs treated with short-term (i.e., 8-32 week) ART, depletion of CD8(+) lymphocytes resulted in increased plasma viremia in all animals and that repopulation of CD8(+) T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4(+) T cells before depletion positively correlated with both the peak and area under the curve of viremia after depletion. These results suggest a role for CD8(+) T cells in controlling viral production during ART, thus providing a rationale for exploring immunotherapeutic approaches in ART-treated HIV-infected individuals.
引用
收藏
页码:656 / 668
页数:13
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