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J. Virol. doi:10.1128/JVI.02748-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Increased Loss of CCR5⁺CD45RA^-CD4⁺ T Cells in CD8⁺ Lymphocyte-depleted Simian Immunodeficiency Virus-infected Rhesus Monkeys

Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana 70433; Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115; Division of Infectious Diseases, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611; Institute of Immunology, Technical University of Dresden, 01101 Dresden, Germany; AIDS Vaccine Program, SAIC Frederick, Inc., National Cancer Institute at Frederick, Frederick, Maryland 21702; Department of Surgery, Duke University Medical Center, SORF Building, LaSalle St. Ext., Durham, North Carolina 27710; and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Maryland 20892

^* To whom correspondence should be addressed. Email: jschmitz{at}bidmc.harvard.edu.

	Abstract

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 compared to controls, suggesting that these SIV target 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.