CD27/CD70 mediated negative regulation of inflammatory T cell response
Bibliographic record
Abstract
Abstract Costimulatory pathways are involved in T cell activation and function. The costimulatory molecule CD27 is a TNF receptor family member expressed on T cells and its ligand, CD70, is known to be expressed on activated antigen-presenting cells, T-, B- and NK cells. The CD27/CD70 pathway has been shown to be critical for T cell activation, differentiation and survival. In this study we have used murine models to study the roles of CD27/CD70 in allogeneic graft-versus-host disease (GVHD) and syngeneic inflammatory bowel disease (IBD). Our results reveal a novel and negative regulatory role played by this pathway as specified in 3 aspects: 1) Allogeneic hematopoietic cell transplantation (allo-HCT) shows that both CD27−/− and CD70−/− donor T cells caused more severe GVHD than WT donor T cells, suggesting that CD27/CD70 signaling in donor T cells inhibits allogeneic T cell response. 2) When transplanted into syngeneic RAG1−/− hosts in an autoimmune IBD model, both CD27−/− and CD70−/− donor CD4+ CD25− T cells caused more severe IBD than WT T cells, suggesting that CD27/CD70 signaling in T cells inhibits autoimmune T cell response. 3) When used as hosts for allo-HCT, both CD27−/− and CD70−/− mice exhibited more severe GVHD compared to WT mice, suggesting that CD27/CD70 signaling in the host inhibits allogeneic T cell response. Mechanistic analyses reveal that this pathway executes immune suppression by limiting T cell expansion and effector function (e.g., TNFa and IFNg production) via a regulatory T cell-independent mechanism that at least partially involves activation-induced T cell death. Overall, our study demonstrates that CD27/CD70 signaling plays a novel role in suppressing allogeneic and autoimmune inflammatory T cell responses.
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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) | 0.001 | 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 | 0.001 |
| 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".