title: Increased loss of CCR5+ CD45RA- CD4+ T cells in CD8+ lymphocyte-depleted Simian immunodeficiency virus-infected rhesus monkeys.
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 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.
authors: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana 70433, USA.
authors: Ronald S
authors: RS
authors: Veazey
authors: Paula M
authors: PM
authors: Acierno
authors: Kimberly J
authors: KJ
authors: McEvers
authors: Susanne H C
authors: SH
authors: Baumeister
authors: Gabriel J
authors: GJ
authors: Foster
authors: Melisa D
authors: MD
authors: Rett
authors: Michael H
authors: MH
authors: Newberg
authors: Marcelo J
authors: MJ
authors: Kuroda
authors: Kenneth
authors: K
authors: Williams
authors: Eun-Young
authors: EY
authors: Kim
authors: Steven M
authors: SM
authors: Wolinsky
authors: E Peter
authors: EP
authors: Rieber
authors: Michael
authors: M
authors: Piatak
authors: Jeffrey D
authors: JD
authors: Lifson
authors: David C
authors: DC
authors: Montefiori
authors: Charles R
authors: CR
authors: Brown
authors: Vanessa M
authors: VM
authors: Hirsch
authors: Jörn E
authors: JE
authors: Schmitz
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D018450:Disease Progression; D015683:Gene Products, gag / Q000276:immunology; D007422:Intestines / Q000166:cytology / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008297:Male; D019713:Receptors, CCR5 / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015996:Survival Rate; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D015683:Gene Products, gag; D019713:Receptors, CCR5; D017493:Leukocyte Common Antigens