T CELL MEDIATED KIDNEY REJECTION INDUCES SELECTIVE LOSS OF EPITHELIAL GENE EXPRESSION BEFORE TUBULITIS DEVELOPS
Bibliographic record
Abstract
P272 Kidney allograft rejection is associated with profound changes in gene expression, which reflect changes in the intrinsic cell population as well as in the infiltrating cells. To relate histology to transcriptional changes during the course of rejection, we analysed mouse kidney transplants from CBA donors into B6 recipients. Interstitial infiltration and edema developed rapidly by day 5 (D5) and evolved slowly thereafter; tubulitis and arteritis were absent at D5 but extensive by D21. All early histologic changes were T cell dependent i.e. unchanged in mice lacking immunoglobulins. Syngeneic transplants did not show any lesions. To explore how the process of rejection alters the expression of kidney genes, we analysed gene expression using Affymetrix MOE 430A microarrays. We defined renal genes as high expressing genes (signal > 1000) in normal kidney (NCBA), assuming that these should reflect changes in the kidney parenchyma. Of 22.690 transcripts on this array, 3424 were highly expressed in NCBA. Following transplantation, there was selective downregulation of some renal genes, with a subset of 118 genes decreased >3 fold at D5. Over time, gene expression either stabilized at a low level or continued a further decrease. None of the downregulated genes recovered by D21. Although in 427 genes downregulation reached significance not before D21, analysis using a QT clustering algorithm showed that in the majority of these genes initial changes in expression level could be noted as early as D5. In syngeneic transplants, downregulation occurred in only 30 genes at D7 without further decrease over time. To simulate the cellular infiltrate during rejection, we spiked RNA from normal kidney with RNA from mixed lymphocyte culture. The added lymphocyte RNA adequately created T cell gene expression similar to that of rejecting grafts but did not significantly reduce the expression of renal genes, indicating that the downregulation of these genes cannot be attributed to dilution by infiltrating cells but reflects changes in the renal epithelium (Table 1).FigureWe observed profound selective changes in genes involved in metabolism, mediation of epithelial function, cytoskeleton organization and cell-cell adhesion. The results suggest that gene expression in the renal parenchyma is selectively altered by the stress of the surgical procedure, but changes are greatly increased by rejection. The infiltration of cells during early T cell mediated kidney rejection may rapidly alter epithelial programs to precipitate loss of function and possibly the early stages of epithelial atrophy. Table 1: Changes in selected T cell genes and high expressing renal genes over the course of rejection and by dilution of kidney RNA with RNA from mixed lymphocyte cultures.
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 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) | 0.001 | 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 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".