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

Johanna Tauriainen, Lydia Scharf, Juliet Frederiksen, Ali Naji, Hans-Gustaf Ljunggren, Anders Sönnerborg, Ole Lund, Gustavo Reyes-Terán, Frederick Mm Hecht, Steven G. Deeks, Michael R. Betts, Marcus Buggert, Annika C. Karlsson

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    Abstract

    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
    Publication statusPublished - 2017

    Cite this

    Tauriainen, J., Scharf, L., Frederiksen, J., Naji, A., Ljunggren, H-G., Sönnerborg, A., Lund, O., Reyes-Terán, G., Hecht, F. M., Deeks, S. G., Betts, M. R., Buggert, M., & Karlsson, A. C. (2017). Perturbed CD8+ T cell TIGIT/CD226/PVR axis despite early initiation of antiretroviral treatment in HIV infected individuals. Scientific Reports, 7, [40354]. https://doi.org/10.1038/srep4035