IVIg-Primed Splenocytes Ameliorate Murine ITP in an MHC Class II-Unrestricted Manner.
Bibliographic record
Abstract
Abstract We have previously demonstrated that IVIg-primed leukocytes can, upon transfer to naïve mice, completley recapitulate the therapeutic effects of IVIg in treating immune thrombocytopenia in a murine model. Dendritic cells (DC) appear to be the primary cellular target of IVIg in this model. The exact pathway by which IVIg-primed DC inhibit platelet clearance remains, however, unknown. DC are professional antigen presenting cells of haematopoietic origin that are specialized for the capture, processing and presentation of antigens to T cells via their MHC Class II. This primary function of DC is absolutely dependent on MHC Class II expression. Herein, we have evaluated the efficacy of action of IVIg-primed splenocytes from MHC mismatched mice in the amelioration of murine ITP. Mice expressing the Class II haplotype I-Ab (C57BL/6) were injected intravenously with IVIg-primed splenocytes from syngeneic mice, or Balb/C mice (Class II haplotype I-Ad /I-Ed) or CD1 mice (outbred, mixed Class II haplotype I-A/E) prior to the induction of thrombocytopenia by an anti-platelet antibody. We found that IVIg-primed splenocytes from all strains of mice tested were able to successfully ameliorate thrombocytopenia in C57BL/6 mice, regardless of Class II haplotype. None of the splenocytes primed with a control protein, BSA, ameliorated thrombocytopenia. To confirm our findings that IVIg-primed splenocytes function independent of MHC haplotype, we next employed IVIg-primed splenocytes from MHC Class II deficient mice and found these splenocytes were also able to successfully ameliorate murine thrombocytopenia. These data demonstrate a non-MHC-restricted function for DC in IVIg function, and suggest that IVIg-primed DC function occurs independent of MHC Class II expression in the amelioration of murine ITP. In addition, since this potential new cell-based therapy for ITP is not MHC-restricted, we speculate that IVIg-primed DC from any donor (including autologous) could theoretically be used to treat individuals with ITP or other autoimmune diseases without the requirement for donor matching.
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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".