Inhibition of Lymphocyte Activation in Response to HLA Derived Peptides in Renal Transplant Recipients.
Bibliographic record
Abstract
Introduction We have previously demonstrated Renal Transplant Recipients (RTR) peripheral blood mononuclear cell (PBMC) responses to non-polymorphic HLA derived peptides; associated with chronic allograft dysfunction. γ interferon (γ-IFN) production to these peptides derives from CD4+CD25HiCD45RO+CD127Hi T lymphocytes, which we now demonstrate is from the CCR7- fraction. The effects of inhibitors of lymphocyte activation on these responses was examined in cell culture. Method PBMC's from 4 RTR already identified to respond to HLA class 1 derived peptides, were enriched with sorted autologous activated memory T cells and cultured in the presence or absence of peptide and of:ciclosporin, sirolimus, abatacept and Shk peptide. Cell culture supernatant cytokine concentrations were analysed at 240 using a multiplex assay and spots enumerated. Results The responses to antigenic peptide are shown as a normalised percentage of that in the absence of the inhibitors. The cytokine responses to the peptides are shown below in the presence of inhibitors.Table: No Caption available.No IL2, IL5 or TNF-α was detected in the presence of Shk peptide, nor ciclosporin at a concentration of 200ng/ml. Significant levels of IL2 & TNF-α were however detected at ciclosporin concentrations of 100ng/ml. Conclusion These data document the production of IL2, TNF-α and γ-IFN, by activated memory cells from RTR in response to non-polymorphic HLA derived peptides. These in vitro responses are effectively abolished in the presence of ciclosporin at a concentration that corresponds to the upper quartile trough concentration in the BENEFIT study (at 1 year) however re-emerge at a concentration that corresponds to the lower quartile (and to the target concentration in the low dose ciclosporin arm in SYMPHONY). These findings illustrate how relatively subtle intra and inter-individual variations in calcineurin inhibitor exposure could influence the emergence of HLA peptide specific T cell memory. They identify potential targets for monitoring and intervention particularly with respect to long term maintenance of immunosuppression. DISCLOSURES:Larche, M.: Other, Circassia, Paid Consultancy. Ball, S.: Other, Circassia, Paid Consultancy.
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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) | 0.002 | 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".