| Title: |
Temporal dynamics of CD8+ T cell effector responses during primary HIV infection. |
| Authors: |
Demers, KR; Makedonas, G; Buggert, M; Eller, MA; Ratcliffe, SJ; Goonetilleke, N; Li, CK; Eller, LA; Rono, K; Maganga, L; Nitayaphan, S; Kibuuka, H; Routy, J-P; Slifka, MK; Haynes, BF; McMichael, AJ; Bernard, NF; Robb, ML; Betts, MR |
| Contributors: |
Douek, DC |
| Publisher Information: |
Public Library of Science |
| Publication Year: |
2018 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
The loss of HIV-specific CD8+ T cell cytolytic function is a primary factor underlying progressive HIV infection, but whether HIV-specific CD8+ T cells initially possess cytolytic effector capacity, and when and why this may be lost during infection, is unclear. Here, we assessed CD8+ T cell functional evolution from primary to chronic HIV infection. We observed a profound expansion of perforin+ CD8+ T cells immediately following HIV infection that quickly waned after acute viremia resolution. Selective expression of the effector-associated transcription factors T-bet and eomesodermin in cytokine-producing HIV-specific CD8+ T cells differentiated HIV-specific from bulk memory CD8+ T cell effector expansion. As infection progressed expression of perforin was maintained in HIV-specific CD8+ T cells with high levels of T-bet, but not necessarily in the population of T-betLo HIV-specific CD8+ T cells that expand as infection progresses. Together, these data demonstrate that while HIV-specific CD8+ T cells in acute HIV infection initially possess cytolytic potential, progressive transcriptional dysregulation leads to the reduced CD8+ T cell perforin expression characteristic of chronic HIV infection. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1371/journal.ppat.1005805 |
| DOI: |
10.1371/journal.ppat.1005805 |
| Availability: |
https://doi.org/10.1371/journal.ppat.1005805; https://ora.ox.ac.uk/objects/uuid:074457a2-6689-4bd5-84a6-dbef18bf85f3 |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Accession Number: |
edsbas.2D26F3F1 |
| Database: |
BASE |