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Journal of Virology, April 2007, p. 3465-3476, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02392-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Subdominant CD8+ T-Cell Responses Are Involved in Durable Control of AIDS Virus Replication{triangledown}

Thomas C. Friedrich,1* Laura E. Valentine,1 Levi J. Yant,2 Eva G. Rakasz,1 Shari M. Piaskowski,1 Jessica R. Furlott,1 Kimberly L. Weisgrau,1 Benjamin Burwitz,1 Gemma E. May,1 Enrique J. León,1 Taeko Soma,1 Gnankang Napoe,1 Saverio V. Capuano III,1 Nancy A. Wilson,1 and David I. Watkins1,2

Wisconsin National Primate Research Center, Madison, Wisconsin 53715,1 Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison, Wisconsin 537062

Received 31 October 2006/ Accepted 16 January 2007

"Elite controllers" are individuals that durably control human immunodeficiency virus or simian immunodeficiency virus replication without therapeutic intervention. The study of these rare individuals may facilitate the definition of a successful immune response to immunodeficiency viruses. Here we describe six Indian-origin rhesus macaques that have controlled replication of the pathogenic virus SIVmac239 for 1 to 5 years. To determine which lymphocyte populations were responsible for this control, we transiently depleted the animals’ CD8+ cells in vivo. This treatment resulted in 100- to 10,000-fold increases in viremia. When the CD8+ cells returned, control was reestablished and the levels of small subsets of previously subdominant CD8+ T cells expanded up to 2,500-fold above predepletion levels. This wave of CD8+ T cells was accompanied by robust Gag-specific CD4 responses. In contrast, CD8+ NK cell frequencies changed no more than threefold. Together, our data suggest that CD8+ T cells targeting a small number of epitopes, along with broad CD4+ T-cell responses, can successfully control the replication of the AIDS virus. It is likely that subdominant CD8+ T-cell populations play a key role in maintaining this control.

* Corresponding author. Mailing address: Wisconsin National Primate Research Center, 1220 Capitol Ct., Madison, WI 53715-1299. Phone: (608) 265-3381. Fax: (608) 265-8084. E-mail: thomasf{at}primate.wisc.edu.

{triangledown} Published ahead of print on 24 January 2007.

Journal of Virology, April 2007, p. 3465-3476, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02392-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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