Effects of in vivo CD8(+) T cell depletion on virus replication in rhesus macaques immunized with a live, attenuated simian immunodeficiency virus vaccine

The role of CD8(+) T lymphocytes in controlling replication of live, attenu ated simian immnunodeficiency virus (SIV) was investigated as part of a vac cine study to examine the correlates of protection in the SIV/rhesus macaqu e model. Rhesus macaques immunized for >2 yr with nef-deleted SIV (SIVmac23 9 Delta nef) and protected from challenge with pathogenic SIVmac251 were tr eated with anti-CD8 antibody (OKT8F) to deplete CD8(+) T cells in vivo. The effects of CD8 depletion on viral load were measured using a novel quantit ative assay based on real-time polymerase chain reaction using molecular be acons. This assay allows simultaneous detection of both the vaccine strain and the challenge virus in the same sample, enabling direct quantification of changes in each viral population. Our results show that CD8(+) T cells w ere depleted within 1 h after administration of OKT8F, and were reduced by as much as 99% in the peripheral blood. CD8(+) T cell depletion was associa ted with a 1-2 log increase in SIVmac239 Delta nef plasma viremia. Control of SIVmac239 Delta nef replication was temporally associated with the recov ery of CD8(+) T cells between days 8 and 10. The challenge virus, SIVmac251 , was not detectable in either the plasma or lymph nodes after depletion of CD8(+) T cells. Overall, our results indicate that CD8(+) T cells play an important role in controlling replication of live, attenuated SIV in vivo.