Quantification of the Relative Importance of CTL, B Cell, NK Cell, and Target Cell Limitation in the Control of Primary SIV-Infection

CD8(+) cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, B cells and target cell limitation have all been suggested to play a role in the control of SIV and HIV-1 infection. However, previous research typically studied each population in isolation leaving the magnitude, relative importance and in vivo relevance of each effect unclear. Here we quantify the relative importance of CTLs, NK cells, B cells and target cell limitation in controlling acute SIV infection in rhesus macaques. Using three different methods, we find that the availability of target cells and CD8(+) T cells are important predictors of viral load dynamics. If CTL are assumed to mediate this anti-viral effect via a lytic mechanism then we estimate that CTL killing is responsible for approximately 40% of productively infected cell death, the remaining cell death being attributable to intrinsic, immune (CD8(+) T cell, NK cell, B cell) -independent mechanisms. Furthermore, we find that NK cells have little impact on the death rate of infected CD4(+) cells and that their net impact is to increase viral load. We hypothesize that NK cells play a detrimental role in SIV infection, possibly by increasing T cell activation.