SIV-specific CD8 T cells with perforin granules located exclusively within cell membranes correlate with the maturation of SIVmac239Δnef vaccine induced protection

Abstract Vaccination with live-attenuated SIVmac239Δnef protects most animals challenged with a pathogenic SIV. In this model, there is a maturation of protection which occurs between 5 and 20 weeks post-vaccination. We previously showed that this maturation of protection did not correlate with distribution or density of SIV-specific CD8 T cells in lymphoid or genital tissues. In this study, we investigated whether the maturation of protection correlated with levels of the effector protein perforin in SIV-specific CD8 T cells in lymphoid or vaginal tissues. Using in situ tetramer staining with MHC tetramers combined with immunohistochemistry, and quantitative image analysis, we quantified perforin levels in SIV-specific CD8 T cells; Perforin negative cells are characterized as central memory T cells (TCM), perforin low cells are effector memory (TEM), and perforin high/med are effector T cells (TEFF). We also quantified a unique population of SIV-specific CD8 T cells with perforin localized exclusively within the cell membrane, which are likely to be a subset of TEM. From 5 to 20 weeks post-infection, we found increase in perforin negative and decrease in perforin high tetramer binding CD8 T cells. We also found an increase in SIV-specific CD8 T cells expressing low levels of perforin located exclusively in the cell membrane that correlated with the maturation of protection. These findings indicate that the maturation of protection induced by SIVmac239Δnef vaccine correlates with a shift from a primary response dominated by effector CD8 T cells, to a memory response, which includes an increase in SIV-specific CD8 T cells with perforin located exclusively in the cell membrane. These findings help inform the development of a successful HIV vaccine.