Immunohistochemical Analysis Reveals an Influx of Regulatory T Cells and Focal Trophoblastic STAT-1 Phosphorylation in Chronic Villitis of Unknown Etiology
Bibliographic record
Abstract
Maternal T cells and fetal macrophages constitute the primary infiltrate of chronic villitis of unknown etiology (CVUE), but the role of CD25(+)/FOXP3(+) regulatory T (Treg) cells in CVUE has not been examined. Moreover, little is known about the expression of immune markers, such as the major histocompatibility complex (MHC) class II antigen, human leukocyte antigen-DR (HLA-DR), in trophoblasts in this disease. We, therefore, examined CVUE placentas for the presence of Treg cells and aberrant activation of HLA-DR in trophoblasts. Sequential formalin-fixed, paraffin-embedded tissue sections from 8 CVUE placentas and 10 control placentas were stained by immunohistochemistry with antibodies for CD3, CD4, CD8, CD20, CD25, FOXP3, CD56, CD68, HLA-DR, STAT-1, and phosphorylated STAT-1 [P-(Y701)-STAT-1]. T cells and histiocytes were confirmed as the inflammatory infiltrate in CVUE. In areas of CVUE, histiocytes strongly expressed HLA-DR and nuclear P-(Y701)-STAT-1, and the relative numbers of CD25(+)/FOXP3(+) Treg cells were increased, compared with control placentas. In 5 of 8 CVUE cases, there was patchy nuclear expression of P-(Y701)-STAT-1 in syncytiotrophoblast most extensively involved by villitis, but no other marker examined was detected in the trophoblast cell layer. We confirmed the influx of T cells and histiocytes in CVUE. Our results are the 1st, to our knowledge, to identify increased numbers of Treg cells in CVUE vs noninflamed placentas. However, we were unable to verify HLA-DR expression in trophoblasts of placentas with CVUE, suggesting that this does not contribute to the influx of T cells. Our observation that P-(Y701)-STAT-1 expression in a syncytiotrophoblast is restricted to regions of inflammation suggests that the JAK-STAT-1 pathway is aberrantly activated in these cells.
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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 | 0.001 | 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) | 0.001 | 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".