Photodepletion differentially affects CD4+ Tregs versus CD4+ effector T cells from patients with chronic graft-versus-host disease
Bibliographic record
Abstract
Even the most potent immunosuppressive drugs often fail to control graft-versus-host disease (GVHD), the most frequent and deleterious posttransplantation complication. We previously reported that photodepletion using dibromorhodamine (TH9402) eliminates T cells from healthy donors activated against major histocompatibility complex-incompatible cells and spares resting T cells. In the present study, we identified photodepletion conditions selectively eradicating endogenous proliferating T cells from chronic GVHD patients, with the concomittant sparing and expansion of CD4(+)CD25(+) forkhead box protein 3-positive T cells. The regulatory T-cell (Treg) nature and function of these photodepletion-resistant cells was demonstrated in coculture and depletion/repletion experiments. The mechanism by which Tregs escape photodepletion involves active P-glycoprotein-mediated drug efflux. This Treg-inhibitory activity is attributable to interleukin-10 secretion, requires cell-cell contact, and implies binding with cytotoxic T-lymphocyte antigen 4 (CTLA-4). Preventing CTLA-4 ligation abrogated the in vitro generation of Tregs, thus identifying CTLA-4-mediated cell-cell contact as a crucial priming event for Treg function. Moreover, the frequency of circulating Tregs increased in chronic GVHD patients treated with TH9402 photodepleted cells. In conclusion, these results identify a novel approach to both preserve and expand Tregs while selectively eliminating CD4(+) effector T cells. They also uncover effector pathways that could be used advantageously for the treatment of patients with refractory GVHD.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 teacher head, 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".