Small intestine and colon tissue-resident memory CD8+ T cells exhibit molecular heterogeneity and differential dependence on Eomesodermin
Bibliographic record
Abstract
Abstract Tissue-resident memory CD8+T (TRM) cells are a subset of memory T cells positioned at barrier sites, critical for host defense against infection. Recent studies have begun to reveal substantial heterogeneity in CD8+ TRM populations across different tissues. The gut consists of four anatomically distinct compartments, the epithelia and lamina propria in the small intestine (siIEL, siLPL) and colon (cIEL, cLPL). While CD8+ TRM in the small intestine epithelia are well-described, findings are often generalized to the whole gut, thus obscuring potential differences in CD8+ TRM in the much-less studied small intestine lamina propria and colon compartments. We thereby characterized CD8+ TRM in the four intestinal layers using single cell RNA-sequencing and flow cytometry. We show that CD8+ TRM across the intestinal compartments exhibit differences in the expression of surface molecules, cytokines, granzymes, and transcription factors. For example, small intestine intraepithelial CD8+ TRM produce the highest levels of granzymes, whereas colon intraepithelial CD8+ TRM have the greatest capacity for cytokine production. We also uncover an unexpected, tissue-specific role for the T-box transcription factor Eomesodermin (Eomes), known to suppress TRM formation in the skin, liver, and kidney. Our data demonstrate that Eomes is dispensable for CD8+ TRM formation in both the small intestine and colon. By contrast, following CD8+ TRM formation, Eomes plays a critical role in promoting the maintenance of established CD8+ TRM in the small intestine, but not in the colon. Together, our study provides new insights into intestinal CD8+ TRM heterogeneity and differential transcriptional regulation of intestinal TRM formation vs. maintenance. Presenting author Y.H.L. is supported by the Canadian Institutes of Health Research (CIHR) Doctoral Foreign Study Award. This study is supported by grants from NIH (P01 AI132122).
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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 | 0.000 |
| 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 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".