A novel SIV gag-specific CD4+T-cell clone suppresses SIVmac239 replication in CD4+T cells revealing the interplay between antiviral effector cells and their infected targets

Abstract

To study CD4+T-cell suppression of AIDS virus replication, we isolated nine rhesus macaque SIVGag-specific CD4+T-cell clones. One responding clone, Gag68, produced a typical cytotoxic CD8+T-cell response: induction of intracellular IFN-γ, MIP-1α, MIP-1β, and CD107a degranulation. Gag68 effectively suppressed the spread of SIVmac239 in CD4+T cells with a corresponding reduction of infected Gag68 effector cells, suggesting that CD4+effectors need to suppress their own infection in addition to their targets to be effective. Gag68 TCR cloning and gene transfer into CD4+T cells enabled additional experiments with this unique specificity after the original clone senesced. Our data supports the idea that CD4+T cells can directly limit AIDS virus spread in T cells. Furthermore, Gag68 TCR transfer into CD4+T-cell clones with differing properties holds promise to better understand the suppressive effector mechanisms used by this important component of the antiviral response using the rhesus macaque model.