Prolongation of Heterotopic Heart Allograft Survival by Portal Venous Injection of Alloantigen: The Role of Hepatic Nonparenchymal Cells
Bibliographic record
Abstract
The induction of immune hyporesponsiveness in transplantation is a complex interaction between the immune system and the alloantigen. The route by which an antigen is introduced to the immune system plays an important role in the immune response. Antigen delivered via the portal circulation has the ability to induce T-cell hyporesponsiveness. In this study we examined the mechanism responsible for the induction of hyporesponsiveness by assessing immune response following portal vein (pv) injection of donor alloantigen. C57B1/6 mice were immunized via pv with splenic mononuclear cells (SMNC) from BALB/c mice. The recipient immune response was assessed in vivo by murine heterotopic heart transplant survival. SMNC and hepatic nonparenchymal cells (NPC) were isolated from pv immunized animals and used as regulatory cells in a one-way mixed lymphocyte culture (MLC) as a measure of in vitro recipient responder SMNC proliferation. Survival of murine heterotopic heart transplants was prolonged following pv injection of alloantigen (p < .04 compared to nonimmunized or systemically immunized mice). Stimulation of responder SMNCs isolated from pv immunized mice resulted in an antigen-specific hyporesponsiveness (p < .05 compared with nonimmunized or systemically immunized mice). Cocultures of responder SMNCs from nonimmunized (naive) mice with hepatic NPC from previously pv immunized mice resulted in attenuation of T-cell proliferation in MLR following stimulation with donor alloantigen (p < .05 compared to coculture with NPC from nonimmunized mice or SMNC from pv immunized mice). These data would suggest that the hepatic NPC plays an important role in the regulation of the immune response. With further identification of cell subtypes responsible for induction of hyporesponsiveness, future therapies may be directed at these specific targets, thereby minimizing the harmful side effects of current immunosuppressive therapies.
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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 | 0.001 |
| 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".