CD8β Depletion Does Not Prevent Control of Viral Replication or Protection from Challenge in Macaques Chronically Infected with a Live Attenuated Simian Immunodeficiency Virus
| Autor: | Gabrielle L. Barry, Alexis J. Balgeman, Thomas C. Friedrich, Nancy J. Sullivan, Annie W. Lau-Kilby, Shelby L. O’Connor, Andrea M. Weiler, Amy L. Ellis-Connell, John R. Mascola, Yan Zhou, Matthew S. Sutton, Rosemarie D. Mason, Scott Hetzel, Kristin K. Biris, Mario Roederer |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
medicine.drug_class
CD8 Antigens T cell Immunology Simian Acquired Immunodeficiency Syndrome Viremia CD8-Positive T-Lymphocytes Biology Virus Replication Monoclonal antibody medicine.disease_cause Microbiology Lymphocyte Depletion Plasma 03 medical and health sciences 0302 clinical medicine T-Lymphocyte Subsets In vivo Virology medicine Animals Lymph node 030304 developmental biology 0303 health sciences Viral Load Simian immunodeficiency virus medicine.disease medicine.anatomical_structure Viral replication Insect Science Macaca Pathogenesis and Immunity Simian Immunodeficiency Virus CD8 030215 immunology |
| Zdroj: | Journal of Virology. 93 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | We evaluated the contribution of CD8αβ(+) T cells to control of live-attenuated simian immunodeficiency virus (LASIV) replication during chronic infection and subsequent protection from pathogenic SIV challenge. Unlike previous reports with a CD8α-specific depleting monoclonal antibody (mAb), the CD8β-specific mAb CD8β255R1 selectively depleted CD8αβ(+) T cells without also depleting non-CD8(+) T cell populations that express CD8α, such as natural killer (NK) cells and γδ T cells. Following infusion with CD8β255R1, plasma viremia transiently increased coincident with declining peripheral CD8αβ(+) T cells. Interestingly, plasma viremia returned to predepletion levels even when peripheral CD8αβ(+) T cells did not. Although depletion of CD8αβ(+) T cells in the lymph node (LN) was incomplete, frequencies of these cells were 3-fold lower (P = 0.006) in animals that received CD8β255R1 than in those that received control IgG. It is possible that these residual SIV-specific CD8αβ(+) T cells may have contributed to suppression of viremia during chronic infection. We also determined whether infusion of CD8β255R1 in the LASIV-vaccinated animals increased their susceptibility to infection following intravenous challenge with pathogenic SIVmac239. We found that 7/8 animals infused with CD8β255R1, and 3/4 animals infused with the control IgG, were resistant to SIVmac239 infection. These results suggest that infusion with CD8β255R1 did not eliminate the protection afforded to LASIV vaccination. This provides a comprehensive description of the impact of CD8β255R1 infusion on the immunological composition in cynomolgus macaques, compared to an isotype-matched control IgG, while showing that the control of LASIV viremia and protection from challenge can occur even after CD8β255R1 administration. IMPORTANCE Studies of SIV-infected macaques that deplete CD8(+) T cells in vivo with monoclonal antibodies have provided compelling evidence for their direct antiviral role. These studies utilized CD8α-specific mAbs that target both the major (CD8αβ(+)) and minor (CD8αα(+)) populations of CD8(+) T cells but additionally deplete non-CD8(+) T cell populations that express CD8α, such as NK cells and γδ T cells. In the current study, we administered the CD8β-specific depleting mAb CD8β255R1 to cynomolgus macaques chronically infected with a LASIV to selectively deplete CD8αβ(+) T cells without removing CD8αα(+) lymphocytes. We evaluated the impact on control of virus replication and protection from pathogenic SIVmac239 challenge. These results underscore the utility of CD8β255R1 for studying the direct contribution of CD8αβ(+) T cells in various disease states. |
| Databáze: | OpenAIRE |
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