Extensive CD8β depletion does not prevent control of viral replication or protection from challenge in macaques chronically infected with a live attenuated simian immunodeficiency virus

Abstract

We evaluated the contribution of CD8{beta}+ T cells on control of live-attenuated simian immunodeficiency virus (LASIV) replication during chronic infection and subsequent protection from pathogenic SIV challenge. Unlike previous reports with a CD8-specific depleting monoclonal antibody (mAb), the CD8{beta}-specific mAb CD8{beta}255R1 selectively depleted CD8{beta}+ T cells without also depleting non-CD8+ T cell populations that express CD8, such as natural killer (NK) cells and {gamma}{delta} T cells. Following infusion with CD8{beta}255R1, plasma viremia transiently increased coincident with declining peripheral CD8{beta}+ T cells. Interestingly, plasma viremia returned to pre-depletion levels even when peripheral CD8{beta}+ T cells did not. Although depletion of CD8{beta}+ T cells in the lymph node (LN) was incomplete, frequencies of these cells were three-fold lower (p=0.006) in animals that received CD8{beta}255R1 compared to control IgG. It is possible that these residual SIV-specific CD8{beta}+ T cells may have contributed to suppression of viremia during chronic infection. We also determined whether infusion of CD8{beta}255R1 in the LASIV-vaccinated animals increased their susceptibility to infection following intravenous challenge with pathogenic SIVmac239. We found that 7/8 animals infused with CD8{beta}255R1, and 3/4 animals infused with the control IgG, were resistant to SIVmac239 infection. These results suggest that infusion with CD8{beta}255R1 did not eliminate the protection afforded to LASIV vaccination. This provides a comprehensive description of the impact of CD8{beta}255R1 infusion on the immunological composition of the host, when compared to an isotype matched control IgG, while showing that the control of LASIV viremia and protection from challenge can occur even after CD8{beta}255R1 administration.\n\nImportanceStudies 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 CD8-specific mAbs that target both the major (CD8{beta}+) and minor (CD8+) populations of CD8+ T cells, but additionally deplete non-CD8+ T cell populations that express CD8, such as NK cells and {gamma}{delta} T cells. In the current study, we administered the CD8{beta}-specific depleting mAb CD8{beta}255R1 to cynomolgus macaques chronically infected with a LASIV to selectively deplete CD8{beta}+ T cells without removing CD8+ lymphocytes. We evaluated the impact on control of virus replication and protection from pathogenic SIVmac239 challenge. These results underscore the utility of CD8{beta}255R1 for studying the direct contribution of CD8{beta}+ T cells in various disease states.