A New Murine Model of Immune Thrombocytopenia: Evidence of Both Antibody- and CD8+ T Cell-Mediated Platelet Destruction.
Bibliographic record
Abstract
Abstract Immune thrombocytopenic purpura (ITP) is an autoimmune-mediated bleeding disorder in which platelets are opsonized by autoantibodies and prematurely destroyed by Fc receptor (R)-mediated phagocytosis in the reticuloendothelial system (RES). Although the pathogenesis of the disorder has been considered to be primarily antibody mediated, recent reports have indicated that cell-mediated (e.g. CD8+ T cell) mechanisms can also lead to platelet destruction at least in those patients with ITP who have no detectible antibodies. To study these mechanisms, we developed a murine model of immune thrombocytopenia by transferring spleen cells (SC) from GPIIIa-knockout (KO) mice immunized against wild type (WT; GPIIIa-positive) platelets into syngeneic severe combined immunodeficient (SCID) mice. Results show that compared with naive SC, transfer of as few as 5x104 immune GPIIIa-KO SC caused significant thrombocytopenia and a bleeding diathesis and death in 60 percent of recipient SCID mice within 10 days post-transfer. Bleeding occurred primarily in the gut, lungs, subcutaneous tissues and brain. When the immune GPIIIa-KO SC were first depleted of CD4+T cells and transferred, thrombocytopenia or bleeding mortality occurred. In contrast, CD8+ T cell depletion of the GPIIIa-KO SC before transfer did not affect their ability to cause thombocytopenia nor bleeding. Interestingly, depletion of CD19+ B cells before transfer did not affect the ability of the SC to induce thrombocytopenia but prevented all bleeding. These results suggest that both antibody-mediated and CD8+ T cell-mediated platelet destruction occur in this animal model of immune thrombocytopenia, however, it appears that only antibody-mediated thrombocytopenia is associated with bleeding mortality. Because the immune thrombocytopenia is against a platelet-specific antigen e.g. GPIIIa (like in ITP), it will not only allow for the study of disease pathogenesis but may also be important for testing new immunospecific therapeutics to increase platelet counts in patients with ITP.
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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) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| 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".