Oral Presentation 8th Australasian Virology Society Meeting and 11th Annual Meeting of the Australian Centre for Hepatitis & HIV Virology Meeting 2015

Dendritic cell-T cell interactions and HIV latency in CD4+ T cells.  (#46)

Paul Cameron 1 2 3 , Renee M van der Sluis 1 2 3 , Vanessa A Evans 1 2 3 , Nitasha A Kumar 1 2 3 , Sharon R Lewin 1 2 3 , Rafik-Pierre Sekaly 4 , Remi Fromentin 4 , Nicola Chomont 4
  1. Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia
  2. Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, VIC, Australia
  3. Centre for Biomedical Research, Burnet Institute, Melbourne, VIC, Australia
  4. VGTI-Vaccine and Gene Therapy Institute Florida, Port St.Lucie, Florida, United States

Background:  Dendritic cells (DC) mediate HIV trans-infection and T cell activation and proliferation during interaction with cognate T cells.  We examined T cells clustering with DC to determine if DC can control HIV expression and latency in non-proliferating T cells. 

Methods:  Resting CD4+ T-cells were isolated from normal blood, labelled with the proliferation dye eFluor670, and cultured alone, or with autologous blood myeloid DC (mDC) for 24h before infection with CCR5-tropic eGFP-reporter virus. Latent infection was determined by sorting for EGFP- T cells after 5 days and activation with anti-CD3/CD28+IL-7 and an integrase inhibitor (L8). We compared mDC to other DC and myeloid sub-populations including plasmacytoid DC (pDC) and monocytes for T cell activation, productive infection and latent HIV infection. Wee also examined expression of immune checkpoints (IC) on T cells and IC ligands on DC.  

Results: Sub-populations of DC and monocytes differed in their ability to induce productive and latent infection in T cells.  CD1c+ mDC, CD141+ DC, SLAN+ DC, and CD14+ monocytes were able to induce both productive and latent infection in the resting non-proliferating T cells. B cells and CD16+ SLAN- monocytes poorly induced latency and pDC were exceptional in not inducing latency and in blocking latency when added back to mDC-T cell cocultures. The pDC inhibition was by a soluble factor blocked by pDC radiation and by antibody to IFNAR. 

IC ligands were expressed on mDC and monocytes.  By sorting for IC on non-proliferating CD4+ T-cells we found significant enrichment for HIV latency in cells positive for PD1, Tim3, CTLA-4 and BTLA but not TIGIT  or LAG3. 

Conclusion:  In this model of HIV latency preferential expression of IC on non-proliferating HIV infected T-cells suggests that DC may generate latency in T cells by controlling T cell activation and HIV expression.