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| Status |
Public on Aug 30, 2021 |
| Title |
Functional impairment of HIV-specific CD8+ T cells precedes aborted control of viremia |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Spontaneous control of HIV infection has been repeatedly linked to antiviral CD8+ T cells but is not always permanent. To address mechanisms of durable and aborted control of viremia, we evaluated immunologic and virologic parameters in longitudinal samples from 34 subjects with differential outcomes. Despite sustained recognition of autologous virus, aborted control was preceded by impairment of HIV-specific proliferative and cytolytic T cell effector functions without evidence of canonical T cell exhaustion. During aborted control, HIV-specific CD8+ T cells infiltrated lymphoid follicles but exhibited poor functionality relative to durable control. Longitudinal transcriptomic profiling of HIV-specific CD8+ T cells revealed altered expression of genes related to T cell activation, cytokine-mediated signaling and cell cycle regulation preceding aborted control, including increased expression of the antiproliferative transcription factor KLF2. Our results identify prognostic indicators of aborted HIV control and elucidate functional requirements for durable immune control, which may guide development of new therapies
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| Overall design |
Longitudinal RNA-seq of replicate HIV-specific CD8+ T cells preceding aborted or durable control (5 subjects each)
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| Contributor(s) |
Urbach J, Collins D, Walker B |
| Citation(s) |
34496223 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AI149704 |
Understanding and Reversing T Cell Dysfunction to Control and Eliminate Persistent HIV Reservoirs |
MASSACHUSETTS GENERAL HOSPITAL |
Bruce D Walker |
| R01 HL134539 |
A systems biology approach to fingerprint HIV immune defense in Elite Controllers |
MASSACHUSETTS GENERAL HOSPITAL |
Xu Yu |
| R37 AI155171 |
Elite controllers as a model for a cure of HIV-1 infection |
MASSACHUSETTS GENERAL HOSPITAL |
Xu Yu |
| K24 AI155233 |
Mentoring in patient-oriented research to finding a cure for HIV-1 infection |
BRIGHAM AND WOMEN'S HOSPITAL |
Mathias Lichterfeld |
| R01 AI152979 |
Selection and Evolution of HIV-1 reservoir cells in blood and tissues |
BRIGHAM AND WOMEN'S HOSPITAL |
Mathias Lichterfeld |
|
| Submission date |
Mar 04, 2021 |
| Last update date |
Feb 09, 2022 |
| Contact name |
Jonathan Morris Urbach |
| E-mail(s) |
jurbach@mgh.harvard.edu
|
| Organization name |
Ragon Institute of MGH, MIT and Harvard
|
| Lab |
Walker
|
| Street address |
400 Technology Sq Rm 851
|
| City |
Cambridge |
| State/province |
Massachusetts |
| ZIP/Postal code |
02139 |
| Country |
USA |
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| Platforms (1) |
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| Samples (74)
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| Relations |
| BioProject |
PRJNA706759 |
| SRA |
SRP309374 |
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