CD8+ T cells from elite controllers recognize and kill HIV abortively infected CD4+ T cells (VIR6P.1168)

Understanding the underlying immunological mechanisms of spontaneous HIV control by HIV+ elite controllers (EC) remains an important step in the development of efficient HIV vaccines and functional cures. To understand control mechanisms triggered by CD8+ T cell we established a system in non-activated peripheral blood mononuclear cells (PBMC) using infectious HIV (NL4.3 IRES GFP) carrying the fusion protein Vpr-Beta lactamase (to assess viral entry) and a staining strategy to study the CD8+ T cell response by flow cytometry. First we showed that non-activated CD4+ T cells are permissive for HIV entry but this leads mostly to abortive infection (b-lac+ GFP-). CD8+ T cells from EC were able to recognize these HIV+ cells, became activated (IFNg+, MIP1b+) and underwent degranulation (CD107a+). This activation was initiated by the presentation of HIV peptides from incoming viruses and HLA-I blockade almost abolished this response. We confirmed by mass spectrometry HIV peptides processed in the cytoplasm of CD4+ cells shortly after HIV entry. These results suggest that the ability of CD8+ T cells to form immunological synapses allows them to be activated by low levels of HIV antigens from incoming particles at the surface of early-infected CD4+ T cells. Killing of abortively HIV-infected cells early after HIV entry might avoid inflammation due to pyroptosis and therefore contribute to HIV control.