Journal article
Perturbed CD8+ T cell TIGIT/CD226/PVR axis despite early initiation of antiretroviral treatment in HIV infected individuals
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.1
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.2
Division of Transplantation, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.3
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.4
Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.5
Centre for Infectious Diseases Research, National Institute of Respiratory Diseases, Mexico City, Mexico.6
Department of Medicine, University of California, San Francisco Positive Health Program, San Francisco General Hospital, San Francisco, CA, United States of America.7
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.8
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.
| Language: | English |
|---|---|
| Publisher: | Nature Publishing Group |
| Year: | 2017 |
| Pages: | 40354 |
| ISSN: | 20452322 |
| Types: | Journal article |
| DOI: | 10.1038/srep40354 |
Adult Antigens, Differentiation, T-Lymphocyte Antiretroviral Therapy, Highly Active CD226 antigen CD8-Positive T-Lymphocytes Female Gene Expression Regulation HIV HIV Infections Humans Male Middle Aged Receptors, Immunologic Receptors, Virus Signal Transduction TIGIT protein, human poliovirus receptor
