Characterization of human soluble Tim-3 and its role in HIV infection (VIR1P.1002)
Bibliographic record
Abstract
Abstract Chronic Human Immunodeficiency Virus Type-1 (HIV) infection results in a loss of HIV-specific CD8+ T cell effector function, termed “exhaustion”, which is mediated, in-part, by the co-inhibitory receptor T-cell immunoglobulin mucin domain-containing protein 3 (Tim-3). Like many other receptors, a soluble form of this protein has been described in human blood plasma. However, this soluble Tim-3 (sTim-3) is poorly characterized and it’s unclear whether it plays a role in HIV pathogenesis. Using a Tim-3 ELISA, we found that levels of sTim-3 were significantly elevated in HIV+ antiretroviral treatment naïve patient plasma compared to healthy controls or HIV+ antiretroviral treated patients, and significantly correlated positively with viral load but not with CD4+ T cell counts. To characterize this construct, we immunoprecipitated the protein from HIV+ patient plasma; western blotting analysis revealed that plasma sTim-3 is the approximate size of the Tim-3 ectodomain. Following detection of sTim-3 from activated PBMCs in culture, no alternatively spliced Tim-3 constructs were observed, however, levels of sTim-3 were abrogated with the inclusion of a matrix metalloproteinase, ADAM10, inhibitor. Further, we showed that this sTim-3 was produced from activated T cells treated with an ADAM10 agonist and was the approximate size of plasma sTim-3. Our results suggest that increasing levels of viral antigen result in increased Tim-3 shedding from the T cell surface during HIV infection.
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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 | 0.001 |
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; 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".