ADOPTIVE TRANSFER OF SPECIFIC SUBSETS OF DENDRITIC CELLS CHANGES THE XENOGRAFT SURVIVAL AND PATTERN OF REJECTION IN A RAT-TO-MOUSE CARDIAC TRANSPLANTATION MODEL
Bibliographic record
Abstract
O53* Aims: Dendritic cells (DCs) are major regulators of both T cell and B cell immune responses. While we have previously demonstrated that Th2 cytokines are detrimental and Th1 cytokines are beneficial to xenograft survival (Nature Medicine 2000), the immunological factors controlling cytokine profiles of anti-xeno responses remain unknown. We previously reported that CD11c+CD8α+ cells (DC1-like) were predominant in C57BL/6 recipients, in which Lewis heart grafts were slowly rejected with typical cell-mediated rejection (CMR) in 21 days. In contrast, CD11c+CD8α −(DC2-like) were predominant in BALB/c mice, in which the Lewis heart grafts were rapidly rejected with typical acute vascular rejection (AVR) in 6 days. These data suggest that DCs may play an important role in navigating xenograft immune responses. The present study was undertaken to elucidate the role of distinct subsets of DCs in controlling xenograft rejection. Methods: Purified CD8α+ or CD8α− DCs isolated from wild type (WT) BALB/c, WT C57BL/6 and IL-12−/−C57BL/6 mice were adoptively transferred into syngenic BALB/c and IL-12−/− or WT C57BL/6 mice, and recipients subsequently received Lewis rat heart grafts heterotopically 2 days after DC transfer. Intragraft cytokine expression and serum levels of anti-donor antibodies were measured by RT-PCR and flow cytometry, respectively. Results: Adoptive transfer of CD8α+ DCs into BALB/c mice shifted the immune response to Th1 with increased ratios of IFN-γ/IL-4 and IL-12/IL-4 mRNA in the grafts, and increased level of Th1 mediated anti-donor IgG2a in the circulation, thereby altering the pattern of rejection from AVR to CMR and significantly prolonging xenograft survival to 14.2 ± 0.8 days, while transfer of CD8α − DCs did not change the pattern of rejection and the grafts were rejected at 6 days. In addition, transfer of exogenous CD8α+ DCs rather than CD8α − DCs from WT C57BL/6 mice into IL-12−/− C57BL/6 mice prevented AVR and prolonged xenograft survival to 16.4 ± 0.9 days, while IL-12−/− C57BL/6 mice without transfer rapidly rejected the xenografts with AVR in 6 days. Furthermore, adoptive transfer of CD8α − DCs from IL-12−/− mice into WT C57BL/6 recipients shifted the immune response to Th2 with decreased ratios of intragraft IFN-γ/IL-4 and IL-12/IL-4 mRNA, but increased level of Th2 mediated anti-donor IgG1, thereby altering the pattern of rejection from CMR to AVR and the grafts were rapidly rejected in 9.5 ± 0.6 days. Conclusions: Transfer of CD8α+ DCs (DC1-like) induces Th1-mediated CMR and prolongs xenograft survival, whereas administration of CD8α − DCs (DC2-like) facilitates Th2-mediated AVR and accelerates xenograft rejection. These data suggest that distinct DC subclasses differentially affect the mechanism of xenograft rejection and ultimately affect graft survival.
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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 | 0.002 |
| 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".