Recovery of Functional EBV Specific T Cells Is Not Impaired In Patients with Chronic Gvhd.
Bibliographic record
Abstract
Abstract Abstract 1286 Introduction: T cell expression of PD-1, a marker of functional exhaustion manifested by inability to produce cytokines upon stimulation, is upregulated in patients with acute GHVD. This is thought to explain at least in part why patients with acute GVHD have frequent infections (Gallez-Hawkins et al, BBMT15:872, 2009). Here we wished to evaluate whether this is true also for chronic GVHD. Patients and Methods: We studied 17 allogeneic HCT recipients for AML who have not developed acute or chronic GVHD by day 84. Their blood was drawn on day 84, 180 and 365. Between day 84 and 365, 7 patients did and 10 patients did not develop chronic GVHD needing systemic immunosuppressive therapy (de novo, ie, without preceding acute GVHD). Onset of the chronic GVHD was on median day 103 (range, 90–147). We studied total CD4 and CD8 T cells as well as Epstein-Barr virus (EBV)-specific CD4 and CD8 T cells, as patients with chronic GVHD are at risk of EBV disease (Landgren et al, Blood,14:4992, 2009). Blood mononuclear cells were stimulated with Epstein-Barr virus (EBV) lysate, EBNA3A+B+C overlapping peptides, no or irrelevant stimulus as negative control, or Staphylococcal enterotoxin B as positive control. After overnight incubation, expression of IFNγ, TNFα, IL2 and PD-1 on CD3+CD4+CD8- or CD3+CD4-CD8+ cells was determined by flow cytometry. Cells expressing IFNγ, TNFα, IL2 or their combinations were enumerated. PD-1 expression was quantified using beads coated with anti-mouse antibody (Quantum Simply Cellular, Bangs Laboratories) and expressed as antibody binding capacity units (ABC) (dynamic range, approximately 300 to 500,000 ABC units per cell). Results: PD-1 expression on total, EBV lysate-specific or EBNA3-specific CD4 or CD8 T cells was not significantly higher among patients who did vs did not develop chronic GVHD. On the contrary, there was a trend toward lower PD-1 expression on EBV lysate-specific CD4 and CD8 T cells and EBNA3-specific CD4 T cells in patients who developed chronic GVHD. This was significant (p<.05, Mann-Whitney test) for EBV lysate-specific CD4 T cells on day 84, EBV lysate-specific CD8 T cells on day 180, EBV lysate-specific CD4 and CD8 T cells on day 365, EBNA3-specific CD4 T cells on day 84 and EBNA3-specific CD4 T cells on day 365. Consistent with that, absolute counts of total, EBV lysate-specific or EBNA3-specific T cells were not significantly lower in patients who did vs did not develop chronic GVHD. On the contrary, there was a trend toward higher EBV lysate-specific and EBNA3-specific CD4 or CD8 T cell counts in patients who developed chronic GVHD. This was significant on day 84 for total EBV lysate-specific CD4 and CD8 cells, EBV lysate-specific CD4+IFNγ+ cells and CD8+IFNγ+ cells, and total EBNA3-specific CD4 cells, EBNA3-specific CD4+IFNγ+ cells, CD4+IL2+ cells, CD4+IFNγ+TNFα+IL2+ cells and CD8+IFNγ+ cells. Conclusion: De novo chronic GvHD and its treatment do not adversely affect the counts of functional EBV specific T cells. Disclosures: No relevant conflicts of interest to declare.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| 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) | 0.003 | 0.001 |
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".