Low levels of SDF-1α constrain DC recovery and diminish homeostatic proliferation of naïve CD4+ T cells during graft-versus-host disease. (TRAN3P.892)
Bibliographic record
Abstract
Abstract Graft-versus-host disease (GVHD) is the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (SCT) and its effect on T cell regeneration greatly increases the immunodeficiency normally associated with SCT. As a result, GVHD patients experience profound lymphopenia and lymphocyte reconstitution takes generally several months or years. The goal of this work was to assess the impact of GVHD on homeostatic proliferation (HP) of non-alloreactive naïve CD4+ T lymphocytes with the hypothesis that regeneration of the peripheral niche permissive to CD4 HP is constrained by GVHD. To study the impact of GVHD on the peripheral niche regulating CD4 HP, we used a Parent→F1 mouse model and observed a complete abrogation of CD4 HP in GVHD hosts. Loss of HP was related to depletion of all DC subsets as well as low levels of IL-7. While Flt3-ligand (FL) levels were normal, Stromal Derived Factor-1α (SDF-1α) was significantly diminished in GVHD mice. Administration of FL or SDF-1α significantly increased DC counts but CD4 HP was restored only when FL or SDF-1α was combined to IL-7. Importantly, while FL treatment aggravated GVHD, GVHD was improved by SDF-1α therapy. Our study shows that lack of immune reconstitution of CD4+ T cells is primarily due to failure of DC recovery owing to diminished SDF-1α production and diminished IL-7 and that the combination of SDF-1α and IL-7 could be used to enhance CD4 HP in GVHD hosts.
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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".