Thymic Retention of CD4+CD25hi+FoxP3+ T Regulatory (Treg) Cells Is Responsible for Peripheral Treg Deficiency and Platelet and Megakaryocyte Destruction in Active Immune Thrombocytopenia (ITP)
Bibliographic record
Abstract
Abstract Abstract 523 Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which antibodies and/or cytotoxic T cells are directed against an individual's own platelets and/or megakaryocytes and lead to enhanced platelet destruction in the periphery and reduced platelet production within the bone marrow. It is becoming increasingly clear that the immune dysregulation leading to ITP is primarily due to T cell disturbances and recently, many reports have demonstrated that active ITP is associated with a peripheral deficiency of tolerance-inducing CD4+CD25+FoxP3+ T regulatory cells (Tregs). Using a murine model of ITP that demonstrates both antibody and T cell-mediated platelet and megakaryocyte destruction, we analyzed the role that Tregs may play in active ITP. BALB/c CD61 knockout (KO) mice were immunized against wildtype (CD61+) platelets and 1.5×104 of their splenocytes were transferred ip into CB.17 severe combined immunodeficient (SCID) mice and their platelet counts, phenotype and percentage of CD4+CD25hi+FoxP3+ Tregs were enumerated in various lymphoid tissues at various times after transfer. Results showed that within 2 weeks post-transfer, 16 of 30 transferred mice became thrombocytopenic (<300×109 platelets/L) whereas the remaining mice did not. Bleeding diatheses and mortality occurred in 4 of the 16 thrombocytopenic mice. Of interest, compared with control SCID mice transferred with naïve BALB/c splenocytes or the non-thrombocytopenic SCID mice, the thrombocytopenic mice had significant elevations in thymic weights and percentages of CD4+CD25hi+FoxP3 Tregs by 2 weeks post transfer. Splenic weights in the thrombocytopenic mice increased but at the same rate as control mice, however, the proportion of Tregs in the spleens were significantly less than control non-thrombocytopenic mice. Treatment of the thrombocytopenic mice with 2g/kg intravenous gammaglobulin (IVIg) raised the platelet counts, reduced thymic weights and normalized both the thymic and splenic Treg populations compared with controls. The results suggest that active ITP in this mouse model is associated with a peripheral (splenic) Treg deficiency due to thymic retention of the Tregs. It proposes a new mechanism of Treg deficiency in ITP; Tregs are withheld from the periphery by thymic sequestration. Disclosures: No relevant conflicts of interest to declare.
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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) | 0.002 | 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".