Specific Elimination of Alloreactive T Lymphocytes Using Photodynamic Therapy Prevents GVHD and Enables Rapid Immune Reconstitution.
Bibliographic record
Abstract
Abstract Graft-versus-host disease (GVHD) and impaired immune reconstitution are the primary obstacles limiting the efficacy of allogeneic stem cell transplantation (SCT). Graft-versus-host disease (GVHD) and impaired immune reconstitution are the primary obstacles limiting the efficacy of allogeneic stem cell transplantation (SCT). The purpose of this study was to determine whether selective depletion of donor alloantigen-specific T lymphocytes using photodynamic therapy (PDT) would prevent GVHD and enable immune reconstitution in the context of MHC-mismatched SCT. This question was addressed in an MHC-incompatible mouse model of GVHD. The donor (C57BL/6; H-2b) derived spleen cells were first activated against C3H/HeJ (H-2k) host spleen cells in a one-way mixed lymphocyte culture and then exposed to photodynamic treatment, using dibromorhodamine methyl ester (TH9402) as a photosensitizer. Activated T cells showed preferential retention of this photosensitizer compared to resting lymphocytes. In addition, in vitro experiments revealed that PDT eradicated a significantly higher proportion of activated than resting T cells. When lethally irradiated H-2k mice (C3H/HeJ and B10BR) were transplanted with C57BL/6 derived T cell-depleted bone marrow cells supplemented with C57BL/6 derived spleen cells activated with C3H/HeJ targets, they rapidly succumbed to acute GVHD (within 10–47 days). In contrast, both mouse strains receiving histoincompatible C57BL/6 T cells previously exposed to PDT after activation against C3H/HeJ survived until the end of the observation period (>100 days)(p<0.0001). Additionally, transplantation of treated T cells induced lethal GVHD in C57BL/6 histoincompatible strains of mice (third party), suggesting PDT specifically eradicated activated T cells while sparing most resting T lymphocytes. Analysis of immune recovery, evaluating T and B cell populations in thymus and spleen, activated T cells components (CD44, CD62L, CD69), proliferative responses (anti-CD3 and conA), and Vβ repertoire indicated that T and B cell reconstitution in MHC-mismatched mice transplanted with treated primed cells was similar to that of mice transplanted with treated or control autologous cells indicating that immune cells were preserved and functional. These results demonstrate that PDT can selectively eliminate alloreactive T cells and prevent the development of GVHD, while sparing T cells reactive against non-host antigens, thus offering protection against infection and disease relapse.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.000 | 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".