Increased Loss of CCR5+CD45RA−CD4+T Cells in CD8+Lymphocyte-Depleted Simian Immunodeficiency Virus-Infected Rhesus Monkeys
Open Access
- 1 June 2008
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 82 (11), 5618-5630
- https://doi.org/10.1128/jvi.02748-07
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.Keywords
This publication has 92 references indexed in Scilit:
- Contribution of CD8+T Cells to Containment of Viral Replication and Emergence of Mutations inMamu-A*01-Restricted Epitopes in Simian Immunodeficiency Virus-Infected Rhesus MonkeysJournal of Virology, 2008
- Use of an anti‐CD16 antibody for in vivo depletion of natural killer cells in rhesus macaquesImmunology, 2008
- HIV turns plasmacytoid dendritic cells (pDC) into TRAIL-expressing killer pDC and down-regulates HIV coreceptors by Toll-like receptor 7-induced IFN-αProceedings of the National Academy of Sciences, 2007
- Flow cytometric detection of degranulation reveals phenotypic heterogeneity of degranulating CMV-specific CD8+ T lymphocytes in rhesus macaquesJournal of Immunological Methods, 2007
- Progressive CD4+ central–memory T cell decline results in CD4+ effector–memory insufficiency and overt disease in chronic SIV infectionThe Journal of Experimental Medicine, 2007
- Unique Pathology in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques Is Consistent with a Pathogenesis Distinct from That of Classical AIDSJournal of Virology, 2007
- Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1Nature Genetics, 2007
- HIV-1 immunopathogenesis: How good interferon turns badClinical Immunology, 2006
- Preferential Infection Shortens the Life Span of Human ImmunodeficiencyVirus-Specific CD4+T Cells In VivoJournal of Virology, 2006
- CD4+ T-cell depletion in HIV infection: Are we closer to understanding the cause?Nature Medicine, 2002