| Title: |
High Number of Activated CD8(+) T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection |
| Authors: |
Kessing, CF; Spudich, S; Valcour, V; Cartwright, P; Chalermchai, T; Fletcher, JLK; Takata, H; Nichols, C; Josey, BJ; Slike, B; Krebs, SJ; Sailsuta, N; Lerdlum, S; Jagodzinski, L; Tipsuk, S; Suttichom, D; Rattanamanee, S; Zetterberg, H; Hellmuth, J; Phanuphak, N; Robb, ML; Michael, NL; Ananworanich, J; Trautmann, L |
| Source: |
JAIDS: Journal of Acquired Immune Deficiency Syndromes , 75 (1) pp. 108-117. (2017) |
| Publisher Information: |
LIPPINCOTT WILLIAMS & WILKINS |
| Publication Year: |
2017 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
HIV; cytotoxic T lymphocytes; HIV-specific CD8+ T cells; neuroinflammation; HIV-associated neurocognitive disorders |
| Description: |
BACKGROUND: Central nervous system (CNS) infiltration by CD8+ T cells is associated with neuroinflammation in many neurodegenerative diseases, including HIV-associated dementia. However, the role of CD8+ T cells in the CNS during acute HIV infection (AHI) is unknown. METHODS: We analyzed the phenotype, gene expression, T cell receptor (TCR) repertoire, and HIV specificity of CD8+ T cells in cerebrospinal fluid (CSF) of a unique cohort captured during the earliest stages of AHI (n = 26), chronic (n = 23), and uninfected (n = 8). RESULTS: CSF CD8+ T cells were elevated in AHI compared with uninfected controls. The frequency of activated CSF CD8+ T cells positively correlated to CSF HIV RNA and to markers of CNS inflammation. In contrast, activated CSF CD8+ T cells during chronic HIV infection were associated with markers of neurological injury and microglial activation. CSF CD8+ T cells in AHI exhibited increased functional gene expression profiles associated with CD8+ T cells effector function, proliferation, and TCR signaling, a unique restricted TCR Vbeta repertoire and contained HIV-specific CD8+ T cells directed to unique HIV epitopes compared with the periphery. CONCLUSIONS: These results suggest that CSF CD8+ T cells in AHI expanding in the CNS are functional and directed against HIV antigens. These cells could thus play a beneficial role protective of injury seen in chronic HIV infection if combination antiretroviral therapy is initiated early. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/1550494/1/Kessing_High_Number_Activated.pdf; https://discovery.ucl.ac.uk/id/eprint/1550494/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/1550494/1/Kessing_High_Number_Activated.pdf; https://discovery.ucl.ac.uk/id/eprint/1550494/ |
| Rights: |
open |
| Accession Number: |
edsbas.45AF1C21 |
| Database: |
BASE |