NDLI: CD160 and PD-1 Co-Expression on HIV-Specific CD8 T Cells Defines a Subset with Advanced Dysfunction

Content Provider	PubMed Central
Author	Peretz, Yoav He, Zhong Shi, Yu Bader, Yassine-diab Goulet, Jean-philippe Bordi, Rebeka Ali, Fil-mouhim Loubert, Jean-baptiste El-far, Mohamed Dupuy, Franck P. Rachid, Boulassel Mohamed Tremblay, Cécile Jean-pierre, Routy Bernard, Nicole Balderas, Robert Haddad, Elias K. Sékaly, Rafick-pierre
Editor	Silvestri, Guido
Copyright Year	2012
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 NFκB 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.
Related Links	http://dx.doi.org/10.1371/journal.ppat.1002840
Starting Page	1002840
File Format	PDF
ISSN	15537374
e-ISSN	15537374
Journal	PLoS Pathogens
Issue Number	8
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2012-08-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Immunology Genetics Molecular Biology Microbiology Parasitology Virology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Virology Molecular Biology Parasitology Immunology Microbiology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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