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

Yoav Peretz, Zhong He, Yu Shi, Bader Yassine-Diab, Jean Philippe Goulet, Rebeka Bordi, Ali Filali-Mouhim, Jean Baptiste Loubert, Mohamed El-Far, Franck P. Dupuy, Mohamed Rachid Boulassel, Cécile Tremblay, Jean Pierre Routy, Nicole Bernard, Robert Balderas, Elias K. Haddad, Rafick Pierre Sékaly

Research output: Contribution to journalArticle

86 Citations (Scopus)

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.

Original languageEnglish
Article numbere1002840
JournalPLoS Pathogens
Volume8
Issue number8
DOIs
Publication statusPublished - Aug 2012

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Cell Death
HIV
T-Lymphocytes
T-Lymphocyte Subsets
Virus Diseases
HIV Infections
Cell Survival
Up-Regulation
Down-Regulation
Cell Proliferation
Cytokines
Ligands
Phenotype

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Peretz, Y., He, Z., Shi, Y., Yassine-Diab, B., Goulet, J. P., Bordi, R., ... Sékaly, R. P. (2012). CD160 and PD-1 Co-Expression on HIV-Specific CD8 T Cells Defines a Subset with Advanced Dysfunction. PLoS Pathogens, 8(8), [e1002840]. https://doi.org/10.1371/journal.ppat.1002840

CD160 and PD-1 Co-Expression on HIV-Specific CD8 T Cells Defines a Subset with Advanced Dysfunction. / Peretz, Yoav; He, Zhong; Shi, Yu; Yassine-Diab, Bader; Goulet, Jean Philippe; Bordi, Rebeka; Filali-Mouhim, Ali; Loubert, Jean Baptiste; El-Far, Mohamed; Dupuy, Franck P.; Boulassel, Mohamed Rachid; Tremblay, Cécile; Routy, Jean Pierre; Bernard, Nicole; Balderas, Robert; Haddad, Elias K.; Sékaly, Rafick Pierre.

In: PLoS Pathogens, Vol. 8, No. 8, e1002840, 08.2012.

Research output: Contribution to journalArticle

Peretz, Y, He, Z, Shi, Y, Yassine-Diab, B, Goulet, JP, Bordi, R, Filali-Mouhim, A, Loubert, JB, El-Far, M, Dupuy, FP, Boulassel, MR, Tremblay, C, Routy, JP, Bernard, N, Balderas, R, Haddad, EK & Sékaly, RP 2012, 'CD160 and PD-1 Co-Expression on HIV-Specific CD8 T Cells Defines a Subset with Advanced Dysfunction', PLoS Pathogens, vol. 8, no. 8, e1002840. https://doi.org/10.1371/journal.ppat.1002840
Peretz, Yoav ; He, Zhong ; Shi, Yu ; Yassine-Diab, Bader ; Goulet, Jean Philippe ; Bordi, Rebeka ; Filali-Mouhim, Ali ; Loubert, Jean Baptiste ; El-Far, Mohamed ; Dupuy, Franck P. ; Boulassel, Mohamed Rachid ; Tremblay, Cécile ; Routy, Jean Pierre ; Bernard, Nicole ; Balderas, Robert ; Haddad, Elias K. ; Sékaly, Rafick Pierre. / CD160 and PD-1 Co-Expression on HIV-Specific CD8 T Cells Defines a Subset with Advanced Dysfunction. In: PLoS Pathogens. 2012 ; Vol. 8, No. 8.
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