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

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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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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., Filali-Mouhim, A., Loubert, J. B., El-Far, M., Dupuy, F. P., Boulassel, M. R., Tremblay, C., Routy, J. P., Bernard, N., Balderas, R., Haddad, E. K., & 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