Inhibitory killer cell immunoglobulin-like receptors strengthen CD8+ T cell-mediated control of HIV-1, HCV, and HTLV-1

Lies Boelen; Bisrat Debebe; Marcos Silveira; Arafa Salam; Julia Makinde; Chrissy H Roberts; Eddie C Y Wang; John Frater; Jill Gilmour; Katie Twigger; Kristin Ladell; Kelly L Miners; Jyothi Jayaraman; James A Traherne; David A Price; Ying Qi; Maureen P Martin; Derek C Macallan; Chloe L Thio; Jacquie Astemborski; Gregory Kirk; Sharyne M Donfield; Susan Buchbinder; Salim I Khakoo; James J Goedert; John Trowsdale; Mary Carrington; Simon Kollnberger; Becca Asquith

doi:10.1126/sciimmunol.aao2892

Inhibitory killer cell immunoglobulin-like receptors strengthen CD8⁺ T cell-mediated control of HIV-1, HCV, and HTLV-1

Sci Immunol. 2018 Nov 9;3(29):eaao2892. doi: 10.1126/sciimmunol.aao2892.

Authors

Lies Boelen¹, Bisrat Debebe¹, Marcos Silveira^{1

2}, Arafa Salam³, Julia Makinde⁴, Chrissy H Roberts⁵, Eddie C Y Wang⁶, John Frater^{7

8}, Jill Gilmour⁴, Katie Twigger¹, Kristin Ladell⁶, Kelly L Miners⁶, Jyothi Jayaraman⁹, James A Traherne⁹, David A Price⁶, Ying Qi¹⁰, Maureen P Martin¹⁰, Derek C Macallan³, Chloe L Thio¹¹, Jacquie Astemborski¹¹, Gregory Kirk¹¹, Sharyne M Donfield¹², Susan Buchbinder¹³, Salim I Khakoo¹⁴, James J Goedert¹⁵, John Trowsdale⁹, Mary Carrington^{10

16}, Simon Kollnberger⁶, Becca Asquith¹⁷

Affiliations

¹ Department of Medicine, Imperial College London, London, UK.
² Faculty of Engineering, São Paulo State University-UNESP, São Paulo, Brazil.
³ Institute for Infection and Immunity, St. George's, University of London, London, UK.
⁴ International AIDS Vaccine Initiative Human Immunology Laboratory, London, UK.
⁵ Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.
⁶ Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK.
⁷ Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁸ Oxford NIHR Biomedical Research Centre, Oxford, UK.
⁹ Immunology Division, Department of Pathology, University of Cambridge, Cambridge, UK.
¹⁰ Cancer and Inflammation Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
¹¹ Johns Hopkins University, Baltimore, MD, USA.
¹² Rho, Chapel Hill, NC, USA.
¹³ San Francisco Department of Public Health, San Francisco, CA, USA.
¹⁴ Faculty of Medicine, University of Southampton, Southampton, UK.
¹⁵ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
¹⁶ Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA.
¹⁷ Department of Medicine, Imperial College London, London, UK. b.asquith@imperial.ac.uk.

Abstract

Killer cell immunoglobulin-like receptors (KIRs) are expressed predominantly on natural killer cells, where they play a key role in the regulation of innate immune responses. Recent studies show that inhibitory KIRs can also affect adaptive T cell-mediated immunity. In mice and in human T cells in vitro, inhibitory KIR ligation enhanced CD8⁺ T cell survival. To investigate the clinical relevance of these observations, we conducted an extensive immunogenetic analysis of multiple independent cohorts of HIV-1-, hepatitis C virus (HCV)-, and human T cell leukemia virus type 1 (HTLV-1)-infected individuals in conjunction with in vitro assays of T cell survival, analysis of ex vivo KIR expression, and mathematical modeling of host-virus dynamics. Our data suggest that functional engagement of inhibitory KIRs enhances the CD8⁺ T cell response against HIV-1, HCV, and HTLV-1 and is a significant determinant of clinical outcome in all three viral infections.

Publication types

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

MeSH terms

CD8-Positive T-Lymphocytes / immunology*
HIV-1 / immunology*
Hepacivirus / immunology*
Human T-lymphotropic virus 1 / immunology*
Humans
Receptors, KIR / immunology*

Substances

Receptors, KIR

Abstract

Publication types

MeSH terms

Substances

Grants and funding