HIV Controllers Exhibit Effective CD8+ T Cell Recognition of HIV-1-Infected Non-activated CD4+ T Cells
Blandine Monel,
Annmarie McKeon,
Pedro Lamothe-Molina,
Priya Jani,
Julie Boucau,
Yovana Pacheco,
R. Brad Jones,
Sylvie Le Gall,
Bruce D. Walker
Affiliations
Blandine Monel
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA
Annmarie McKeon
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA
Pedro Lamothe-Molina
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA
Priya Jani
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA
Julie Boucau
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA
Yovana Pacheco
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA; Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
R. Brad Jones
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA; Division of Infectious Diseases, Weill Cornell Medicine, New York, NY 10065, USA
Sylvie Le Gall
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA
Bruce D. Walker
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Corresponding author
Summary: Even with sustained antiretroviral therapy, resting CD4+ T cells remain a persistent reservoir of HIV infection, representing a critical barrier to curing HIV. Here, we demonstrate that CD8+ T cells recognize infected, non-activated CD4+ T cells in the absence of de novo protein production, as measured by immune synapse formation, degranulation, cytokine production, and killing of infected cells. Immune recognition is induced by HLA-I presentation of peptides derived from incoming viral particles, and recognition occurred either following cell-free virus infection or following cell-to-cell spread. CD8+ T cells from HIV controllers mediate more effective immune recognition than CD8+ T cells from progressors. These results indicate that non-activated HIV-infected CD4+ T cells can be targeted by CD8+ T cells directly after HIV entry, before reverse transcription, and thus before the establishment of latency, and suggest a mechanism whereby the immune response may reduce the size of the HIV reservoir. : The cure for HIV is not achievable due to HIV reservoirs, mostly in resting CD4+ T cells. Monel et al. show that CD8+ T cells from HIV controllers are able to establish immunological synapses with HIV+ resting CD4+ T cells, leading to IFN-γ, MIP1-β production, degranulation, and the elimination of the target cells. Keywords: HIV cure, cytotoxic T lymphocytes, HLA, elite controllers, HIV, perforin, granzyme, immunologic synapse
