ResearchIn-Press PreviewAIDS/HIV Open Access | 10.1172/jci.insight.174168
1Barrier Immunity Section, National Institutes of Health, Bethesda, United States of America
2Human Immunology Section, National Institutes of Health, Bethesda, United States of America
3Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
4AIDS and Cancer Virus Program, National Institutes of Health, Frederick, United States of America
5AIDS and Cancer Virus Program, National Institutes of Health, Fredrick, United States of America
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1Barrier Immunity Section, National Institutes of Health, Bethesda, United States of America
2Human Immunology Section, National Institutes of Health, Bethesda, United States of America
3Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
4AIDS and Cancer Virus Program, National Institutes of Health, Frederick, United States of America
5AIDS and Cancer Virus Program, National Institutes of Health, Fredrick, United States of America
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1Barrier Immunity Section, National Institutes of Health, Bethesda, United States of America
2Human Immunology Section, National Institutes of Health, Bethesda, United States of America
3Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
4AIDS and Cancer Virus Program, National Institutes of Health, Frederick, United States of America
5AIDS and Cancer Virus Program, National Institutes of Health, Fredrick, United States of America
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1Barrier Immunity Section, National Institutes of Health, Bethesda, United States of America
2Human Immunology Section, National Institutes of Health, Bethesda, United States of America
3Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
4AIDS and Cancer Virus Program, National Institutes of Health, Frederick, United States of America
5AIDS and Cancer Virus Program, National Institutes of Health, Fredrick, United States of America
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1Barrier Immunity Section, National Institutes of Health, Bethesda, United States of America
2Human Immunology Section, National Institutes of Health, Bethesda, United States of America
3Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
4AIDS and Cancer Virus Program, National Institutes of Health, Frederick, United States of America
5AIDS and Cancer Virus Program, National Institutes of Health, Fredrick, United States of America
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1Barrier Immunity Section, National Institutes of Health, Bethesda, United States of America
2Human Immunology Section, National Institutes of Health, Bethesda, United States of America
3Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
4AIDS and Cancer Virus Program, National Institutes of Health, Frederick, United States of America
5AIDS and Cancer Virus Program, National Institutes of Health, Fredrick, United States of America
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1Barrier Immunity Section, National Institutes of Health, Bethesda, United States of America
2Human Immunology Section, National Institutes of Health, Bethesda, United States of America
3Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
4AIDS and Cancer Virus Program, National Institutes of Health, Frederick, United States of America
5AIDS and Cancer Virus Program, National Institutes of Health, Fredrick, United States of America
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1Barrier Immunity Section, National Institutes of Health, Bethesda, United States of America
2Human Immunology Section, National Institutes of Health, Bethesda, United States of America
3Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
4AIDS and Cancer Virus Program, National Institutes of Health, Frederick, United States of America
5AIDS and Cancer Virus Program, National Institutes of Health, Fredrick, United States of America
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1Barrier Immunity Section, National Institutes of Health, Bethesda, United States of America
2Human Immunology Section, National Institutes of Health, Bethesda, United States of America
3Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
4AIDS and Cancer Virus Program, National Institutes of Health, Frederick, United States of America
5AIDS and Cancer Virus Program, National Institutes of Health, Fredrick, United States of America
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1Barrier Immunity Section, National Institutes of Health, Bethesda, United States of America
2Human Immunology Section, National Institutes of Health, Bethesda, United States of America
3Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
4AIDS and Cancer Virus Program, National Institutes of Health, Frederick, United States of America
5AIDS and Cancer Virus Program, National Institutes of Health, Fredrick, United States of America
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1Barrier Immunity Section, National Institutes of Health, Bethesda, United States of America
2Human Immunology Section, National Institutes of Health, Bethesda, United States of America
3Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
4AIDS and Cancer Virus Program, National Institutes of Health, Frederick, United States of America
5AIDS and Cancer Virus Program, National Institutes of Health, Fredrick, United States of America
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Published June 17, 2024 - More info
Antibody-mediated depletion studies have demonstrated that CD8+ T cells are required for effective immune control of SIV. However, this approach is confounded by several factors, including reactive CD4+ T cell proliferation, and further provides no specificity information. We circumvented these limitations by selectively depleting CD8+ T cells specific for the Gag epitope CTPYDINQM (CM9) via the administration of immunotoxin-conjugated tetrameric complexes of CM9/Mamu-A*01. Immunotoxin administration effectively depleted circulating but not tissuelocalized CM9-specific CD8+ T cells, akin to the bulk depletion pattern observed with antibodies directed against CD8. However, we found no evidence to indicate that circulating CM9-specific CD8+ T cells suppressed viral replication in Mamu-A*01+ rhesus macaques during acute or chronic progressive infection with a pathogenic strain of SIV. This observation extended to macaques with established infection during and after continuous antiretroviral therapy. In contrast, natural controller macaques experienced dramatic increases in plasma viremia after immunotoxin administration, highlighting the importance of CD8+ T cell-mediated immunity against CM9. Collectively, these data showed that CM9-specific CD8+ T cells were necessary but not sufficient for robust immune control of SIV in a nonhuman primate model and, more generally, validated an approach that could inform the design of next-generation vaccines against HIV-1.