Therapeutic CD8 <sup>+</sup> T cell tissue retention and immunomodulation during ART interruption fail to prevent SIV rebound
Bibliographic record
Abstract
A primary obstacle for HIV elimination is the long-term viral reservoir in lymphoid tissues (LT) that can cause rebound viremia if therapy is stopped. Cytotoxic CD8 + T cells are critical for control of HIV and Simian immunodeficiency virus (SIV) viremia; however, CD8 + T cells that migrate to LT are primarily noncytotoxic, calling into question whether these cells could reduce the viral reservoir on antiretroviral therapy (ART) or control viral replication when therapy is halted. To determine whether CD8 + T cells can inhibit viral replication when retained in LT, we inhibited lymphocyte egress from LTs in ART-treated SIV-infected rhesus macaques (RMs) during analytic treatment interruption (ATI) using the S1PR modulator FTY720 alone or in combination with anti-PD1 antibody (αPD1) and the IL-15 receptor superagonist N-803 to increase cytolytic function. FTY720 retained migrating CD4 + and CD8 + T cells in LT, whereas cytotoxic CD8 + T cells remained in the vasculature. After ATI and viral rebound, activated SIV-specific CD8 + T cells increased in frequency in LT of FTY720-treated RMs but failed to become cytotoxic or control plasma viremia compared to controls, even when combined with αPD1 and N-803. These findings indicate that LT-localized CD8 + T cells alone may be insufficient to delay or prevent plasma viral rebound during ATI.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".