Enhancement of Human Immunodeficiency Virus-Specific CD8+ T Cell Responses with TIGIT Blockade Involves Trogocytosis
Bibliographic record
Abstract
Natural killer (NK) and CD8+ T cell function is compromised in human immunodeficiency virus type 1 (HIV-1) infection by increased expression of inhibitory receptors such as TIGIT (T cell immunoreceptor with Ig and ITIM domains). Blocking inhibitory receptors or their ligands with monoclonal antibodies (mAb) has potential to improve antiviral immunity in general and facilitate HIV eradication strategies. We assessed the impact of TIGIT engagement and blockade on cytotoxicity, degranulation, and interferon-gamma (IFN-γ) production by CD8+ T cells from persons living with HIV (PLWH). The effect of TIGIT engagement on non-specific anti-CD3-redirected cytotoxicity was assessed in redirected cytotoxicity assays, and the effect of TIGIT blockade on HIV-specific CD8+ T cell responses was assessed by flow cytometry. In 14/19 cases where peripheral blood mononuclear cells (PBMC) mediated >10% redirected cytotoxicity, TIGIT engagement reduced the level of cytotoxicity to <90% of control values. We selected PLWH with >1000 HIV Gag or Nef-specific IFN-γ spot forming cells per million PBMC to quantify the effects of TIGIT blockade on HIV-specific CD8+ T cell responses by flow cytometry. Cell surface TIGIT expression decreased on CD8+ T cells from 23/40 PLWH following TIGIT blockade and this loss was associated with increased anti-TIGIT mAb fluorescence on monocytes. In total, 6 of these 23 PLWH had enhanced HIV-specific CD8+ T cell degranulation and IFN-γ production with TIGIT blockade, compared to 0/17 with no decrease in cell surface TIGIT expression. Reduced CD8+ T cell TIGIT expression with TIGIT blockade involved trogocytosis by circulating monocytes, suggesting that an effector monocyte population and intact fragment crystallizable (Fc) functions are required for mAb-based TIGIT blockade to effectively enhance HIV-specific CD8+ T cell responses.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.003 | 0.001 |
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; both teacher heads agree on what is shown here.
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".