Sensitization to MHC Antigen Is Characterized By Heightened Early Proinflammatory Cytokine Release Rather Than Lymphocyte Proliferation: Implications for Sensitization After Allograft Rejection.
Bibliographic record
Abstract
Purpose: This study aims to evaluate lymphocyte proliferation and cytokine production in response to mismatched MHC antigen in a mouse model of sensitization. Methods: Two consecutive skin grafts at 14-day interval were performed on C57BL/6 (H2kb) recipients using allogeneic (H2kd) or syngeneic (H2kb) donors. 14 days after the second graft, recipient spleens were harvested for mixed lymphocyte culture (MLC) with T-cell-depleted H2kd splenocytes, for 6h, 24h, 72h and 5 days. At each time-point, intracytoplasmic cytokine expression in recipient splenocytes and their proliferation by CFSE dilution were assessed using flow cytometry. Cytokine release was measured in the supernatant using Luminex. Results: Allogeneic, but not syngeneic, recipients became sensitized, as evidenced by antibody binding to H2kd splenocytes. Following MLC, proliferation did not significantly differ between sensitized (S) and non-sensitized (NS) groups over 5 days (Figure 1, p>0.05). Although percentages of CD4+IL-6+ (S:1.14%, NS:1.66%; p=0.13), CD4+IFN-γ+ (S:5.29%, NS:6.41%; p=0.51) and CD4+IL-4+ (S:1.63%, NS:2.65%; p=0.13) cells were not different at 24h, sensitized cells released higher concentrations of IL-6, IL-4 and IFN-γ than the non-sensitized (Figure 2). Sensitized cells also released IL-17A sharply at 72h, unlike the non-sensitized, even though the percentages of CD4+IL-17A+ cells were not significantly different at 72h (S:3.90%, NS:3.32%; p=0.28). Conclusion: These results suggest that sensitization to MHC antigen is not marked by a difference in lymphocyte proliferation or their expression of pro-inflammatory cytokines, but by the individual cell release of pro-inflammatory cytokines, particularly those involved in the IFN-γ and IL-6/IL-17 pathways.Figure: No Caption available.Figure: No Caption available.DISCLOSURES:Sahakian, S.: Grant/Research Support, Astellas Pharma Canada, Inc. Tchervenkov, J.: Grant/Research Support, Astellas Pharma Canada Inc.
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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) | 0.001 | 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 | 0.000 |
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".