Journal article
CD160 and PD-1 Co-Expression on HIV-Specific CD8 T Cells Defines a Subset with Advanced Dysfunction
PLoS pathogens, v 8(8), pp e1002840-e1002840
01 Aug 2012
PMID: 22916009
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Chronic viral infections lead to persistent CD8 T cell activation and functional exhaustion. Expression of programmed cell death-1 (PD-1) has been associated to CD8 T cell dysfunction in HIV infection. Herein we report that another negative regulator of T cell activation, CD160, was also upregulated on HIV-specific CD8 T lymphocytes mostly during the chronic phase of infection. CD8 T cells that expressed CD160 or PD-1 were still functional whereas co-expression of CD160 and PD-1 on CD8 T cells defined a novel subset with all the characteristics of functionally exhausted T cells. Blocking the interaction of CD160 with HVEM, its natural ligand, increased HIV-specific CD8(+) T cell proliferation and cytokine production. Transcriptional profiling showed that CD160(-)PD-1(+)CD8 T cells encompassed a subset of CD8(+) T cells with activated transcriptional programs, while CD160(+)PD-1(+)T cells encompassed primarily CD8(+) T cells with an exhausted phenotype. The transcriptional profile of CD160(+)PD-1(+)T cells showed the downregulation of the NF kappa B transcriptional node and the upregulation of several inhibitors of T cell survival and function. Overall, we show that CD160 and PD-1 expressing subsets allow differentiating between activated and exhausted CD8 T cells further reinforcing the notion that restoration of function will require multipronged approaches that target several negative regulators.
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Details
- Title
- CD160 and PD-1 Co-Expression on HIV-Specific CD8 T Cells Defines a Subset with Advanced Dysfunction
- Creators
- Yoav Peretz - Caprion (Canada)Zhong He - Vaccine & Gene Therapy Institute of FloridaYu Shi - Vaccine & Gene Therapy Institute of FloridaBader Yassine-Diab - Université de MontréalJean-Philippe Goulet - Université de MontréalRebeka Bordi - Vaccine & Gene Therapy Institute of FloridaAli Filali-Mouhim - Vaccine & Gene Therapy Institute of FloridaJean-Baptiste Loubert - Université de MontréalMohamed El-Far - Université de MontréalFranck P. Dupuy - Vaccine & Gene Therapy Institute of FloridaMohamed Rachid Boulassel - McGill University Health CentreCecile Tremblay - Université de MontréalJean-Pierre Routy - McGill University Health CentreNicole Bernard - McGill UniversityRobert Balderas - BD Biosciences (United States)Elias K. Haddad - Université de MontréalRafick-Pierre Sekaly - Centre Hospitalier de l’Université de Montréal
- Publication Details
- PLoS pathogens, v 8(8), pp e1002840-e1002840
- Publisher
- Public Library Science
- Number of pages
- 13
- Grant note
- P01AI080192 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P01AI080192 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Defining the Pathogenesis of Immune Deficiency in Chronic HIV Infection NIH P01 AI076174 / US National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Nurse Practitioner Master of Science in Nursing (MSN); Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000308558000018
- Scopus ID
- 2-s2.0-84866176745
- Other Identifier
- 991020100061204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Microbiology
- Parasitology
- Virology