Abstract 32: Vγ6+ γδ T cells protect against angiotensin II-induced hypertension and vascular injury in male mice
Bibliographic record
Abstract
Background: γδ T cells mediate angiotensin II (AngII)-induced blood pressure (BP) elevation, vascular injury and activated T cell infiltration in mesenteric vessels with adherent perivascular adipose tissue (MV/PVAT). γδ T cells expressing specific T cell receptor (TCR) variable (V) chain γ develop in several waves in the thymus and migrate to diverse tissues. We hypothesized that γδ T cells expressing specific Vγ subtypes in perivascular tissue are implicated in AngII detrimental hypertensive effects. Methods: C57BL/6J male mice were infused or not with AngII (490 ng/kg/min, SC) for 14 days. Vγ1 and Vγ2 (Vγ1/2)+, Vγ4+, Vγ5+, Vγ6+, and Vγ7+ γδ T cell frequencies and T cell phenotypes were determined by flow cytometry in the spleen, descending thoracic aorta (DTAo)/PVAT, and MV/PVAT (n=7-13). Other sets of AngII-infused mice were injected with control or anti-Vγ6 (n=7-12) or Vγ4 antibodies (n=5-8). BP was determined by telemetry, mesenteric artery (MA) function and remodeling by pressurized myography, and T cell phenotypes by flow cytometry. Results: In DTAo/PVAT and MV/PVAT, respectively, 43±5% and 51%±6% of γδ T cells were Vγ6+, and 17±2% and 23±4% Vγ4+, whereas in the spleen, 36±2% of the γδ T cells were Vγ1/2+, 32±1% Vγ4+ and 24±1% Vγ6+. AngII increased the frequency of Vγ6+ γδ T cells in the spleen (0.8±0.1 vs 0.5±0.0% of CD3, P<0.001) and DTAo/PVAT (5.9±0.8 vs 3.6±0.5% of CD3, P<0.05), and tended to increase their frequency in MV/PVAT. The majority of Vγ6+ γδ T cells were activated (CD69+) in DTAo/PVAT (75±5%) and MV/PVAT (84±2%). Vγ6+ γδ T cell depletion caused a steeper BP elevation (P<0.05) and worsened MA endothelial dysfunction (maximal acetylcholine relaxation response: 28±3 vs 55±8%, P<0.05) in mice infused with AngII. This was associated with increased CD69+ non-Vγ6+ γδ T cells in DTAo/PVAT (3.0±0.7 vs 0.8±0.4% of CD3, P<0.01) and MV/PVAT (15.2±2.6 vs 4.9±1.0% of CD3, P<0.01). Depletion of Vγ4+ γδ T cells in perivascular tissues, did not alter the AngII detrimental effects. Conclusions: Vγ6+ γδ T cells are the most abundant γδ T cell Vγ subtype in perivascular tissues. AngII increased Vγ6+ γδ T cells in the spleen and perivascular tissue. Vγ6+ γδ T cell depletion in AngII-infused mice induced a steeper BP elevation, worsened MA endothelial dysfunction, and activated non-Vγ6+ γδ T cells. Vg6+ γδ T cells may play a protective role in AngII-induced hypertension and vascular injury.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".