Rhesus Cytomegalovirus-Specific CD8+ Cytotoxic T Lymphocytes Do Not Become Functionally Exhausted in Chronic SIVmac239 Infection

Abstract

Rosen et al. CTL Functionality in RhCMV/SIVmac239 Co-infection terminally differentiated effector memory phenotype (CD28 − CCR7 −) during chronic SIVmac239 infection. These results suggest that, in contrast to SIVmac239-specific CTLs, RhCMV-specific CTLs maintain their phenotypes and cytolytic effector functions during chronic SIVmac239 infection, and that retargeting RhCMV-specific CTLs might be a promising SIV immunotherapeutic strategy.

Multiple modes of antigen exposure induce clonotypically diverse epitope-specific CD8+ T cells across multiple tissues in nonhuman primates

“…To assess the TCR repertoire of CMV-specific CD8 + T cells, we sampled rhesus macaques expressing the Mamu A*02 allele and who had acquired CMV infection naturally. CMV-specific CD8 + T cells were identified by MHC-I tetramers containing the Mamu A*02 restricted immunodominant epitopes AN10 (TTRSLEYKN) and VY9 (VTTLGMALY) [ 24 ]. There were no statistically significant differences in the frequencies of AN10- or VY9-specific CD8 + T cells between different anatomical sites ( Fig 4A and 4B ) in the animals we studied, though they tended to be lower in LNs compared to other anatomical sites.…”

“…SIV-specific CD8 + T cells were identified by CM9 (CTPYDINQM; residues 181–189 of SIV Gag protein) conjugated MHC Class I Pentamers (Proimmune). CMV-specific CD8 + T cells were identified by AN10 (TTRSLEYKN, residues 279–288 of CMV IE2 protein) and VY9 (VTTLGMALY, residues 134–142 of CMV IE1 protein) MHC-I Pentamers (NIH tetramer facility and ProImmune respectively) [ 24 ]. All tetramers were conjugated to the APC fluorophore.…”