| Emergence of simian immunodeficiency virus-specific cytotoxic CD4+ T cells and increased humoral responses correlate with control of rebounding viremia in CD8-depleted macaques infected with Rev-independent live-attenuated simian immunodeficiency virus. | |
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MedLine Citation:
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PMID: 20702730 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Indian rhesus macaques infected with the Rev-independent live-attenuated SIVmac239 strains control viremia to undetectable levels, have persistent but low cellular and humoral anti-SIV responses, and show no signs of immune deficiency. To analyze the immune mechanisms responsible for viral control, five macaques infected at day 1 after birth were subjected to CD8(+) cell depletion at 6.7 y postinfection. This resulted in viremia increases to 3.7-5.5 log(10) RNA copies, supporting a role of CD8-mediated responses in the control of viral replication. The rebounding viremia was rapidly controlled to levels below the threshold of detection, and occurred in the absence of SIV-specific CD8(+) T cells and significant CD8(+) T cell recovery in four of the five animals, suggesting that other mechanisms are involved in the immunological control of viremia. Monitoring immune responses at the time of viral control demonstrated a burst of circulating SIV-specific CD4(+) T cells characterized as CD45RA(-)CD28(+)CD95(+)CCR7(-) and also granzyme B(+), suggesting cytotoxic ability. Control of viremia was also concomitant with increases in humoral responses to Gag and Env, including a transient increase in neutralizing Abs against the neutralization-resistant SIVmac239 in four of five animals. These data demonstrate that a combination of cellular responses mediated by CD4(+) T cells and humoral responses was associated with the rapid control of the rebounding viremia in macaques infected by the Rev-independent live-attenuated SIV, even in the absence of measurable SIV-specific CD8(+) T cells in the blood, emphasizing the importance of different components of the immune response for full control of SIV infection. |
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Authors:
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Agneta von Gegerfelt; Antonio Valentin; Candido Alicea; Koen K A Van Rompay; Marta L Marthas; David C Montefiori; George N Pavlakis; Barbara K Felber |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural Date: 2010-08-11 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-03 Completed Date: 2010-11-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 3348-58 Citation Subset: AIM; IM |
Affiliation:
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Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Neutralizing / biosynthesis, physiology Antibodies, Viral / biosynthesis*, physiology CD4-Positive T-Lymphocytes / immunology*, pathology, virology CD8-Positive T-Lymphocytes / immunology*, pathology, virology Cytotoxicity, Immunologic Epitopes, T-Lymphocyte / physiology Genes, env / immunology* Lymphocyte Depletion* Macaca mulatta SAIDS Vaccines / administration & dosage, immunology Simian Acquired Immunodeficiency Syndrome / immunology, pathology, prevention & control* Simian immunodeficiency virus / genetics, immunology* Up-Regulation / immunology* Vaccines, Attenuated / administration & dosage, immunology Viremia / immunology, pathology, prevention & control* Virus Replication / immunology |
| Grant Support | |
ID/Acronym/Agency:
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RR-00169/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Neutralizing; 0/Antibodies, Viral; 0/Epitopes, T-Lymphocyte; 0/SAIDS Vaccines; 0/Vaccines, Attenuated |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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