Abstract 075: The Role of Immunological CD8+ Effector Memory T Cells In Hypertension
Bibliographic record
Abstract
Immunological memory is an important component of adaptive immunity. We have previously shown that T cells are important in hypertension. We therefore hypothesized that memory T cells contribute to long-term and repeated hypertensive challenges. To test this, mice received 2 weeks of angiotensin II, were allowed to recover for 3 weeks and then were received a low dose of ang II (140 ng/kg/min) that minimally raises blood pressure in naïve mice. This low-dose of ang II increased blood pressure to 137±6 mmHg in mice that had previously received a vehicle infusion, but to 172±12 mmHg in mice that had received ang II. In another model we treated mice with L-NAME (0.5mg/ml) in drinking water for two weeks, and then fed a high salt diet (4% NaCl) two weeks after stopping L-NAME. The high salt diet had no effect on blood pressure in naïve mice, but increased blood pressure to 150±6 mmHg in mice that had received L-NAME. In keeping with a memory T cell response, we found that either the ang II or L-NAME and high salt protocols increased CD8+ effector memory cells in the kidney by 4-fold while reducing these effector memory CD8+ T cells in the spleen by 3-fold. CD8+ memory T cells require co-stimulatory signaling between CD70 on macrophages and CD27 on T cells. We found that ang II infusion increased CD70 mRNA in isolated kidney vessels by 5 to 10-fold. Similarly, flow cytometry revealed that ang II increased macrophages expressing CD70 and CD8+ T cells expressing CD27 expression in the kidney. Preliminary results show that anti-CD70 partially blocked memory formation by reducing the hypertensive response to the second low-dose of ang II by about 20 mmHg. Thus, these studies indicate that repeated exposures to ang II promote an immune memory response of CD8+ T cells and markedly enhance the hypertensive response. The role of CD27 and CD70 signaling requires additional study but might serve as a therapeutic target.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".