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

作者：Tauriainen Johanna; Scharf Lydia; Frederiksen Juliet; Naji Ali; Ljunggren Hans Gustaf; Sonnerborg Anders; Lund Ole; Reyes Teran Gustavo; Hecht Frederick M; Deeks Steven G; Betts Michael R; Buggert Marcus; Karlsson Annika C^*

来源：Scientific Reports, 2017, 7(1): 40354.

DOI：10.1038/srep4035

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.

• 出版日期2017-1-13