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*

*المؤلف المقابل لهذا العمل

نتاج البحث: المساهمة في مجلةArticleمراجعة النظراء

120 اقتباسات (Scopus)


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.

اللغة الأصليةEnglish
رقم المقالe1002840
دوريةPLoS Pathogens
مستوى الصوت8
رقم الإصدار8
المعرِّفات الرقمية للأشياء
حالة النشرPublished - أغسطس 2012
منشور خارجيًانعم

ASJC Scopus subject areas

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