LAG3 regulates antibody responses following kidney transplantation
Bibliographic record
Abstract
Abstract Lymphocyte activation gene-3 (LAG3) is a coinhibitory receptor expressed by a range of immune cells. The immunomodulatory potential of LAG3 is being explored in cancer and autoimmunity fields but not in transplantation. Using our mouse kidney transplant models we sought to address the role of LAG3 in graft rejection. Untransplanted LAG3-/- mice have elevated heterologous immunity against a panel of alloantigens. Recipient LAG3 deficiency results in rapid rejection of MHC-mismatched renal allografts that are spontaneously accepted by WT recipients, with graft histology characteristic of antibody mediated rejection (ABMR). Antagonistic LAG3 antibody treatment of WT recipients enhanced anti-donor immune responses and induced kidney damage typical of chronic rejection, indicating that LAG3 regulates de novo alloresponses. Recipient B cell depletion, but not CD8+ T cells, prevented kidney allograft rejection in LAG3-/- recipients further supporting ABMR as the mechanism of graft loss. Posttransplant, follicular T cells and plasma cells are among LAG3 expressing immune cells. To identify the mechanism we used T or B cell conditional LAG3 knockout recipients, neither reject the allograft but both had elevated levels of donor specific antibodies (DSA), indicating LAG3 expression on either T or B cells is sufficient to regulate anti-donor humoral immunity. Our results identify LAG3 as a regulator of DSA following kidney transplantation and a potential therapeutic target for ABMR.
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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 | 0.001 | 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".