Perturbed CD8+ T cell TIGIT/CD226/PVR axis despite early initiation of antiretroviral treatment in HIV infected individuals

Publication: Research - peer-reviewJournal article – Annual report year: 2017

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  • Author: Tauriainen, Johanna

    Karolinska University Hospital, Sweden

  • Author: Scharf, Lydia

    Karolinska University Hospital, Sweden

  • Author: Frederiksen, Juliet

    Department of Bio and Health Informatics, Technical University of Denmark

  • Author: Naji, Ali

    University of Pennsylvania, United States

  • Author: Ljunggren, Hans-Gustaf

    Karolinska University Hospital, Sweden

  • Author: Sönnerborg, Anders

    Karolinska University Hospital, Sweden

  • Author: Lund, Ole

    Genomic Epidemiology, Department of Bio and Health Informatics, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Reyes-Terán, Gustavo

    National Institute of Respiratory Diseases, Mexico

  • Author: Hecht, Frederick Mm

    University of California, United States

  • Author: Deeks, Steven G.

    University of California, United States

  • Author: Betts, Michael R.

    University of Pennsylvania, United States

  • Author: Buggert, Marcus

    University of Pennsylvania, United States

  • Author: Karlsson, Annika C.

    Karolinska University Hospital, Sweden

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HIV-specific CD8+ T cells demonstrate an exhausted phenotype associated with increased expression of inhibitory receptors, decreased functional capacity, and a skewed transcriptional profile, which are only partially restored by antiretroviral treatment (ART). Expression levels of the inhibitory receptor, T cell immunoglobulin and ITIM domain (TIGIT), the co-stimulatory receptor CD226 and their ligand PVR are altered in viral infections and cancer. However, the extent to which the TIGIT/CD226/PVR-axis is affected by HIV-infection has not been characterized. Here, we report that TIGIT expression increased over time despite early initiation of ART. HIV-specific CD8+ T cells were almost exclusively TIGIT+, had an inverse expression of the transcription factors T-bet and Eomes and co-expressed PD-1, CD160 and 2B4. HIV-specific TIGIThi cells were negatively correlated with polyfunctionality and displayed a diminished expression of CD226. Furthermore, expression of PVR was increased on CD4+ T cells, especially T follicular helper (Tfh) cells, in HIV-infected lymph nodes. These results depict a skewing of the TIGIT/CD226 axis from CD226 co-stimulation towards TIGIT-mediated inhibition of CD8+ T cells, despite early ART. These findings highlight the importance of the TIGIT/CD226/PVR axis as an immune checkpoint barrier that could hinder future "cure" strategies requiring potent HIV-specific CD8+ T cells.
Original languageEnglish
Article number40354
JournalScientific Reports
Volume7
Number of pages14
ISSN2045-2322
DOIs
StatePublished - 2017
CitationsWeb of Science® Times Cited: No match on DOI
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