Role of PD-L1/PD-L2 expression by human brain endothelial cells in regulating T cell responses in the context of Multiple Sclerosis. (44.6)
Bibliographic record
Abstract
Abstract T lymphocytes have been implicated in the CNS injury observed in Multiple Sclerosis (MS), an inflammatory disease of the central nervous system (CNS). Engagement of Programmed Death-1 (PD-1), expressed on activated T cells, by its ligands (PD-L1 or PD-L2) suppresses T cell responses. We have previously shown that PD-L1 is upregulated on human CNS glial cells upon inflammation both in vitro and in MS lesions. We observed that several infiltrating CD8 T cells are devoid of PD-1 in MS lesions. Whether human brain endothelial cells (HBECs) which sit at the CNS entrance also express PD-L1 or PD-L2 and thereby block PD-1+ cells migration into CNS has not been established. We assess the expression of PD-L1 and PD-L2 by HBECs and establish its impact on immune responses. Under basal condition, PD-L2 is already highly expressed by HBECs, while PD-L1 is not detected. After stimulation with pro-inflammatory cytokines mimicking MS CNS environment, both proteins are significantly upregulated to similar levels. Blocking PD-L1/2 on HBECs leads to enhanced alloreactive CD4 and CD8 T cell responses in coculture assays and increased migration of CD4 and CD8 T cells using an in vitro model of the blood brain barrier. Our results show that PD-L1 and PD-L2 are both expressed by HBECs upon pro-inflammatory stimuli, and that HBECs-provided PD-L1/2 molecules have a role in dampening T cell responses, as well as in blocking T cell migration into the CNS.
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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) | 0.001 | 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".