Adoptive transfer of double negative T regulatory cells induces B‐cell death in vivo and alters rejection pattern of rat‐to‐mouse heart transplantation
Bibliographic record
Abstract
BACKGROUND: Antibody-mediated hyperacute and acute graft rejection are major obstacles in achieving long-term graft survival in xenotransplantation. It is well documented that regulatory T (Treg) cells play a very important role in regulating immune responses to self and non-self antigens. Our previous studies have shown that TCRalphabeta+CD3+CD4-CD8- (double negative, DN)-Treg cells can suppress anti-donor T-cell responses and prolong graft survival in allo- and xenotransplantation models. We have demonstrated that DN-Treg cells can induce B-cell apoptosis in vitro through a perforin-dependent pathway. METHODS: B6 mice received rat heart grafts, followed by 14 days of LF15-0195 treatment. Some mice received Lewis rat cell activated DN-Treg cells after LF treatment. DN-Treg cells, purified from perforin-/- mice and from B6 mice pre-immunized with third party rat cells, were used as controls. RESULTS: In this study, we investigated the possibility that adoptive transfer of xenoreactive DN-Treg cells could suppress B cells in vivo, thus prolonging xenograft survival. We found that apoptotic death of B cells significantly increased after adoptive transfer of DN-Treg cells. In addition, anti-donor IgG subtypes were significantly inhibited in the DN-Treg cell-treated group, in which the rejection pattern was altered towards cellular-mediated rejection rather than antibody-mediated acute vascular rejection. However, perforin-deficient DN-Treg cells failed to induce B-cell death and to prolong heart graft survival, indicating a perforin-dependent mechanism contributes to B-cell death in vivo. CONCLUSIONS: This study suggests that adoptive transfer of xenoreactive DN-Treg cells can inhibit B-cell responses in vivo. DN-Treg cells may be valuable in controlling B-cell responses in xenotransplantation.
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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 | 0.001 | 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".