Comparison of abacavir‐specific effector and proliferating functions of CD8 T cells in abacavir‐treated HIV‐1 patients
Bibliographic record
Abstract
Abstract Susceptibility to abacavir hypersensitivity (ABH) in HIV‐1‐positive patients is strongly linked to the carriage of HLA‐B*57:01 and the potential mechanism includes drug‐specific activation of cytokine producing CD8 T cells exclusively in individuals carrying HLA‐B*57:01. Here, we report a detailed characterization of abacavir‐induced functional response of CD8 T cells in HLA‐B*57:01pos individuals. Peripheral blood mononuclear cells (PBMNCs) from HLA‐B*57:01posABHpos and HLA‐B*57:01negABHneg individuals were stimulated with abacavir. Multicolor flow cytometry was performed to assess the cytokine (IFNγ) production and degranulation (CD107a expression) after 6–18 hr culture and to enumerate proliferating CD4/CD8 T cells by culturing carboxyfluorescein diacetate succinimidyl ester‐loaded PBMNCs for 7 days. CD8 T cells from HLA‐B*57:01posABHpos individuals were multifunctional: proliferating, IFNγ producing, degranulating (CD107apos), and both degranulating and IFNγ producing (CD107aposIFNγpos). Degranulating CD8 T cells in general and both degranulating and IFNγ producing CD8 T cells in particular dominated abacavir‐specific immune response. All functional responses were partially blocked by addition of HLA‐B*57:01‐reactive Bw4 mAb, but not by non‐HLA‐B*57:01‐reactive Bw6 mAb. In conclusion, the study demonstrates that abacavir‐specific CD8 T‐cell‐restricted immune response in HLA‐B*57:01posABHpos HIV‐1 patients has multiple effector and proliferating functions, where the primary effector response appears to be the release of cytolytic granules. The findings have implications for immunotherapy of HLA‐related drug hypersensitivities.
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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) | 0.002 | 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".