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Journal of Virology, June 2008, p. 5618-5630, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.02748-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Increased Loss of CCR5⁺ CD45RA^– CD4⁺ T Cells in CD8⁺ Lymphocyte-Depleted Simian Immunodeficiency Virus-Infected Rhesus Monkeys

Ronald S. Veazey,¹ Paula M. Acierno,² Kimberly J. McEvers,² Susanne H. C. Baumeister,² Gabriel J. Foster,² Melisa D. Rett,² Michael H. Newberg,² Marcelo J. Kuroda,¹ Kenneth Williams,² Eun-Young Kim,³ Steven M. Wolinsky,³ E. Peter Rieber,⁴ Michael Piatak Jr.,⁵ Jeffrey D. Lifson,⁵ David C. Montefiori,⁶ Charles R. Brown,⁷ Vanessa M. Hirsch,⁷ and Jörn E. Schmitz^2*

Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana 70433,¹ Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115,² Division of Infectious Diseases, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611,³ Institute of Immunology, Technical University of Dresden, 01101 Dresden, Germany,⁴ AIDS Vaccine Program, SAIC Frederick, Inc., National Cancer Institute at Frederick, Frederick, Maryland 21702,⁵ Department of Surgery, Duke University Medical Center, SORF Building, LaSalle Street Extension, Durham, North Carolina 27710,⁶ Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892⁷

Received 27 December 2007/ Accepted 11 March 2008

Previously we have shown that CD8⁺ T cells are critical for containment of simian immunodeficiency virus (SIV) viremia and that rapid and profound depletion of CD4⁺ T cells occurs in the intestinal tract of acutely infected macaques. To determine the impact of SIV-specific CD8⁺ T-cell responses on the magnitude of the CD4⁺ T-cell depletion, we investigated the effect of CD8⁺ lymphocyte depletion during primary SIV infection on CD4⁺ T-cell subsets and function in peripheral blood, lymph nodes, and intestinal tissues. In peripheral blood, CD8⁺ lymphocyte-depletion changed the dynamics of CD4⁺ T-cell loss, resulting in a more pronounced loss 2 weeks after infection, followed by a temporal rebound approximately 2 months after infection, when absolute numbers of CD4⁺ T cells were restored to baseline levels. These CD4⁺ T cells showed a markedly skewed phenotype, however, as there were decreased levels of memory cells in CD8⁺ lymphocyte-depleted macaques compared to controls. In intestinal tissues and lymph nodes, we observed a significantly higher loss of CCR5⁺ CD45RA^– CD4⁺ T cells in CD8⁺ lymphocyte-depleted macaques than in controls, suggesting that these SIV-targeted CD4⁺ T cells were eliminated more efficiently in CD8⁺ lymphocyte-depleted animals. Also, CD8⁺ lymphocyte depletion significantly affected the ability to generate SIV Gag-specific CD4⁺ T-cell responses and neutralizing antibodies. These results reemphasize that SIV-specific CD8⁺ T-cell responses are absolutely critical to initiate at least partial control of SIV infection.

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* Corresponding author. Mailing address: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, RE-213D, 41 Avenue Louis Pasteur, Boston, MA 02115. Phone: (617) 667-5206. Fax: (617) 667-8210. E-mail: jschmitz{at}bidmc.harvard.edu

Published ahead of print on 26 March 2008.

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Journal of Virology, June 2008, p. 5618-5630, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.02748-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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