Tubular cell HIV-entry through apoptosed CD4 T cells: a novel pathway

Abstract

We hypothesized that HIV-1 may enter tubular cells by phagocytosis of apoptotic fragments of HIV-1-infected T cells infiltrating tubular interstitium. The study was designed to evaluate the interaction of programmed death-1 (PD-1) receptors on CD4 T cells and programmed death ligand-1 (PD-L1) on tubular cells (HK2 and HRPTEC, primary tubular cells). Co-cultivation of HIV-1 infected lymphocytes (HIV-LY) with HK2s/HRPTECs resulted in T cell apoptosis, uptake of the apoptosed HIV-LY by HK2s/HRPTECs, tubular cell activation and HIV expression. Cytochalasin-B inhibited tubular cell HIV-LY uptake and anti-PD-L1 antibody inhibited HIV-LY apoptosis and tubular cell HIV-LY uptake, activation and HIV expression. These observations do indicate induction of apoptosis of T cells due to interaction of PD-1 and PD-L1 upon co-cultivation and subsequent phygocytosis of HIV-laden apoptotic bodies by tubular cells and thus the transfer of HIV-1 into tubular cells. These findings identify a novel pathway that facilitates HIV-1 entry into tubular cell.