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Perturbed CD8+ T ce...
Perturbed CD8+ T cell TIGIT/CD226/PVR axis despite early initiation of antiretroviral treatment in HIV infected individuals
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Tauriainen, J (author)
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- Scharf, L (author)
- Karolinska Institutet
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Frederiksen, J (author)
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Naji, A (author)
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- Ljunggren, HG (author)
- Karolinska Institutet
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- Sonnerborg, A (author)
- Karolinska Institutet
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Lund, O (author)
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Reyes-Teran, G (author)
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Hecht, FM (author)
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Deeks, SG (author)
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Betts, MR (author)
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- Buggert, M (author)
- Karolinska Institutet
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- Karlsson, AC (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2017-01-13
- 2017
- English.
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7, s. 40354-
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https://www.nature.c...
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https://doi.org/10.1...
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Abstract
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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.
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Tauriainen, J
-
Scharf, L
-
Frederiksen, J
-
Naji, A
-
Ljunggren, HG
-
Sonnerborg, A
-
show more...
-
Lund, O
-
Reyes-Teran, G
-
Hecht, FM
-
Deeks, SG
-
Betts, MR
-
Buggert, M
-
Karlsson, AC
-
show less...
- Articles in the publication
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Scientific repor ...
- By the university
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Karolinska Institutet