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

doi:10.1016/j.celrep.2019.03.016

HIV Controllers Exhibit Effective CD8⁺ T Cell Recognition of HIV-1-Infected Non-activated CD4⁺ T Cells

Cell Rep. 2019 Apr 2;27(1):142-153.e4. doi: 10.1016/j.celrep.2019.03.016.

Authors

Blandine Monel¹, Annmarie McKeon², Pedro Lamothe-Molina¹, Priya Jani², Julie Boucau², Yovana Pacheco³, R Brad Jones⁴, Sylvie Le Gall², Bruce D Walker⁵

Affiliations

¹ 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.
² Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA.
³ 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.
⁴ 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.
⁵ 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. Electronic address: bwalker@mgh.harvard.edu.

Abstract

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.

Keywords: HIV; HIV cure; HLA; cytotoxic T lymphocytes; elite controllers; granzyme; immunologic synapse; perforin.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

CD4-Positive T-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / virology*
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / pathology
Cells, Cultured
Disease Progression
HEK293 Cells
HIV Infections / immunology*
HIV Infections / pathology*
HIV Infections / therapy
HIV Infections / virology
HIV-1 / immunology*
HIV-1 / physiology
HeLa Cells
Humans
Immunity, Cellular / physiology*
Lymphocyte Activation / physiology
Viral Load / drug effects
Viral Load / immunology
Virus Replication / physiology

Abstract

Publication types

MeSH terms

Grants and funding