Abstract 646: A Critical Role of CD8+ T cells in the Genesis of Renal Dysfunction in Hypertension
Bibliographic record
Abstract
T cells have been implicated in the genesis of hypertension however the mechanisms and subtype of T cells involved are still poorly understood. Moreover, the manner by which T cells of various subtypes affect renal function remains poorly defined. Recently, we found that CD8 + T cells play a critical role in the blood pressure elevation caused by angiotensin II. We sought to determine if CD8 + T cells have a role in the renal responses to angiotensin II. In metabolic chamber studies, we found that wild-type mice excrete 80% of a saline load (10% of body weight) in 4 hours, and that this is decreased in response to angiotensin II to 60 ± 5% (p < 0.05) in WT mice but not in CD8 -/- mice. In contrast, CD4 -/- mice demonstrate a markedly exaggerated anti-natriuretic and anti-diuretic response to angiotensin II (p < 0.001). We also found that chronic angiotensin II infusion increases superoxide production in the renal cortex of WT and CD4 -/- mice, but not in CD8 -/- mice. In addition, we found that angiotensin II infusion caused significant hypertrophy of the renal arterioles (< 25 μm diameter) as reflected by an increase in the media/lumen ratio in wild type and CD4 -/- mice, (1.5 to 4.5 and 2.9 to 5.3 respectively, p < 0.05 for each), but to a lesser extent in CD8 -/- mice (1.8 to 3.3). We also observed that the number of arterioles 0-25 micron in diameter decreased from 16.5 and 15.5 to 11.8 and to 11.4/mm2 in wild type and CD4 -/- mice respectively in response to angiotensin II, but was not changed in CD8 -/- mice. Our study therefore shows a previously unrecognized role for CD8 + T cells in modulating renal sodium and volume retention, renal cortical superoxide production, vascular hypertrophy and rarefaction. Thus, CD8 + T cells are an important intermediate in the actions of angiotensin II on the kidney, and a potential 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".