TY - JOUR
T1 - CD160 and PD-1 Co-Expression on HIV-Specific CD8 T Cells Defines a Subset with Advanced Dysfunction
AU - Peretz, Yoav
AU - He, Zhong
AU - Shi, Yu
AU - Yassine-Diab, Bader
AU - Goulet, Jean Philippe
AU - Bordi, Rebeka
AU - Filali-Mouhim, Ali
AU - Loubert, Jean Baptiste
AU - El-Far, Mohamed
AU - Dupuy, Franck P.
AU - Boulassel, Mohamed Rachid
AU - Tremblay, Cécile
AU - Routy, Jean Pierre
AU - Bernard, Nicole
AU - Balderas, Robert
AU - Haddad, Elias K.
AU - Sékaly, Rafick Pierre
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.ppat.1002840
DO - 10.1371/journal.ppat.1002840
M3 - Article
C2 - 22916009
AN - SCOPUS:84866176745
SN - 1553-7366
VL - 8
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 8
M1 - e1002840
ER -