BTLA signaling is needed in newly generated T cells to block autoimmunity
Bibliographic record
Abstract
Abstract Radiotherapy and/or chemotherapy in cancer treatment causes lymphopenia, which favors autoimmunity. Also, coinhibitory receptor blockade triggers immune-related adverse events in more patients than it cures of cancer. Having shown that PD-1 coinhibitory receptor is required in newly generated T cells (NGTC) to prevent lymphopenia-induced autoimmunity, our objective was to determine if the coinhibitory receptor BTLA is also required to establish tolerance in NGTC during lymphopenia. NGTC from thymocytes or established T cells from splenocytes of wildtype (WT) or BTLA−/− B6 mice were adoptively transferred to lymphopenic Rag−/− B6 mice. Sorted WT or BTLA−/− CD8 or CD4 single-positive (SP) thymocytes were adoptively transferred to Rag−/− mice not expressing MHC II (CiiTA−/−) or lacking MHC I (KbDb−/−), respectively. Disease was assessed by macroscopic appearance and weight loss. About 65% (5/8) recipients of BTLA−/− NGTC developed overt autoimmunity, while 4/4 recipients of BTLA−/− splenocytes were disease-free. 10/10 recipients of BTLA−/− CD8 SP T cells showed progressive weight gain. In contrast, 11/11 BTLA−/− CD4 SP T cell recipients had diarrhea, piloerection, hunched appearance, and progressive weight loss from 3–8 weeks post thymocyte transfer (p<0.0001). 3/11 BTLA−/− CD4 SP T cell recipients developed dermatitis post thymocyte transfer. Overt autoimmunity was evident in all WT Rag−/− (n=11) and Rag−/− KbDb−/− (n=4) recipients of thymocytes, but not in any of the CiiTA−/− recipients (n=4). There were no signs of disease in the recipients of WT NGTC. Our study suggests that BTLA is required to establish tolerance in NGTC. Disease in BTLA−/− thymocyte recipients was mediated by the CD4+ T cells and was dependent on MHC II.
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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) | 0.000 | 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 | 0.001 |
| 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".