CD8+ T cell-mediated inhibition of HIV-1.

Abstract

Abstract CD8+ T cells contribute to the control of viral infections, including HIV-1. Previous studies have reported that CD8+-mediated virus inhibition is predictive of subsequent HIV plasma viremia and CD4+T cell decline in HIV-infected, antiretroviral naïve individuals; higher virus inhibition is associated with a better clinical outcomes. Ex vivo CD8+ T cell-mediated inhibition of HIV replication is measured after co-culture of CD8+ T cells with HIV-1 super-infected, autologous CD4+ T cells, at different effector to target ratios. We adapted and standardized the CD8+ T cell virus inhibition assay (CD8-VIA) for use as an endpoint assay in therapeutic testing of HIV-1 T cell vaccines. CD8+ T cells from HIV infected, durably (>2 years) antiretroviral suppressed participants (n=11) were co-cultured with JR-CSF infected autologous CD4+ T cells at E:T ratios ranging from 1/2:1 to 1/160:1, generating CD8+ T cell virus inhibition curves for each participant. IC50 values varied by 100-fold across participants suggesting that CD8+ T cells harbor a broad range of virus inhibitory capacity even when viremia in participants is durably suppressed. Ongoing studies are comparing IC50 values to other measurements (magnitude, specificity, avidity, proliferation and production of cytokines and lytic molecules) of HIV-specific T cell immunity to understand the critical determinants of CD8+ T cell inhibitory capacity.