425.4: The Role of Role of Sex and T Cells in Natural vs Induced ABO Antibody Production in Mice
Bibliographic record
Abstract
Introduction: Interaction of ‘natural’ ABO antibodies (nAbs) with their cognate AB(H)-antigens (Ags) poses a high risk of rapid rejection of ABO-incompatible (ABOi) organ transplants. We previously demonstrated that a clear understanding of factors influencing ABO nAbs is crucial for successful ABOi heart transplantation. Here we investigated anti-A nAbs vs. intentionally. Methods: Adult wild-type (WT) and CD4 T cell knock-out (CD4KO) mice (C57BL/6 (B6) background) received weekly i.p. injection x3 of human ABO-A blood cell membranes (Hu-A BCM; 100ul of 10% v/v) or left untreated. Serum anti-A Ab was measured by hemagglutination assay using ABO-A erythrocytes from our A-transgenic mouse line. To test for T cell help and/or suppression, sex-matched CD4+ T cells (8-12×106/mouse) or CD4+CD25+ T cells (1.7-2.8×106/mouse) from spleens of WT mice were transferred to CD4KO mice. After adoptive transfer, CD4+ T cell reconstitution in peripheral blood was confirmed and mice were left untreated or challenged with Hu-A BCM and assessed for anti-A Ab. Results: In contrast to WT mice, untreated CD4KO females produced dramatically more anti-A than males, rising substantially with puberty, and this was significantly suppressed in both sexes by adoptive transfer of sex-matched CD4+ T cells. Unlike WT mice, attempted sensitization of CD4KO mice with Hu-A BCM failed to induce additional anti-A beyond the already high levels in either sex; CD4+ T cell adoptive transfer rendered CD4KO mice responsive to A-sensitization. CD4+CD25+ T cell transfer into CD4KO mice neither suppressed anti-A nAbs nor rendered them responsive to A-sensitization (Figure). Conclusions: When ABO ‘natural’ antibodies are discriminated from intentionally induced Abs, several important findings emerge: 1) Anti-A nAbs are produced without CD4+ T cell help in a sex- and age-dependent manner, suggestive of a role for sex hormones in regulating anti-A nAbs. 2) CD4+ T cells, but not CD4+CD25+ regulatory T cells, down-regulate anti-A nAb production. 3) In contrast to anti-A nAbs, production of anti-A iAbs was CD4+ T cell-dependent without a sex bias.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.015 | 0.004 |
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".