Regulatory KIR <sup>+</sup> CD8 <sup>+</sup> T cells are elevated during human pregnancy
Bibliographic record
Abstract
During pregnancy, immune responses must balance protection from infections with tolerance of the semiallogeneic fetus. However, the mechanisms regulating maternal-fetal tolerance remain poorly understood. Recently, we identified CD8 + T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) as a regulatory subset important for suppressing self-reactivity in human autoimmune and infectious diseases. To better understand what other roles these cells might play, we asked whether they are active during pregnancy. We first observed an increased frequency of KIR + CD8 + T cells in the peripheral blood of pregnant people in the second trimester, especially in those carrying a male fetus. In vitro, KIR + CD8 + T cells inhibited the alloreactive responses of maternal T cells against irradiated cord blood cells and selectively suppressed CD8 + T cells targeting male-specific proteins in mothers with male pregnancies. Therefore, the higher induction of KIR + CD8 + T cells in mothers carrying a male fetus may help suppress additional allogeneic responses triggered by male-specific alloantigens. Longitudinal analysis showed that KIR + CD8 + T cells undergo expansion and differentiate into functional cytotoxic cells during pregnancy. Single-cell RNA sequencing of decidual CD8 + T cells from early pregnancy revealed elevated numbers and increased expression of activation markers in KIR + CD8 + T cells at the maternal-fetal interface. In addition, a higher frequency of KIR + CD8 + T cells was associated with spontaneous abortion and preeclampsia. Together, our findings suggest that KIR + CD8 + T cells may contribute to maternal tolerance by modulating fetal-specific alloreactive T cell responses. They may also be useful as candidate biomarkers or therapeutic targets for human pregnancy disorders.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".