CD4(+) T-lymphocytes exhibit biphasic kinetics post-myocardial infarction.
CD4(+) T-lymphocytes exhibit biphasic kinetics post-myocardial infarction.
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DOI：
10.3389/fcvm.2022.992653
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发表时间：
2022
影响因子：
3.6
通讯作者：
Bansal, Shyam S.
中科院分区：
文献类型：
--
作者：
Kumar, Vinay;Prabhu, Sumanth D.;Bansal, Shyam S.
CD 4 + T细胞促进心肌梗死（MI）后的伤口愈合，但促进缺血性心力衰竭（HF; MI后8周）期间的左心室（LV）重塑。因此，了解持续的CD4 + T细胞活化是否导致这种病理反应，或者表型不同的T细胞是否在MI与HF期间被活化是至关重要的。使用流式细胞术，我们发现，心脏的CD4 + T细胞表现出两种不同的模式的迁移。第一种模式包括快速的CD4 + T细胞应答，在MI后3天观察到最大水平，14天恢复至基线水平。然而，在HF期间，我们观察到活化的第二阶段，并且与假手术小鼠相比，HF中的CD4 + T细胞高出约20倍。重要的是，在所有主要T细胞亚群（例如Th 1、Th 2、Th 17和调节性T细胞）中观察到这些双相动力学，表明存在全球变化。为了确定T细胞活化的第二个峰的作用，产生CD4-iDTR小鼠，并从MI后28天开始每10天用DT处理，以在慢性HF期间消耗CD4 + T细胞。虽然同窝对照小鼠显示MI后4 - 8周收缩末期和舒张末期容积（ESV和EDV）增加和射血分数（EF）降低，但Cre+小鼠中CD4 + T细胞的耗竭显著减弱LV重塑，并抑制EDV和ESV的进行性增加以及EF的降低。这表明HF期间发生的CD4 + T细胞应答与MI期间发生的应答不同，并促进LV重塑和进行性心功能不全。CD4 + T细胞的时间免疫调节可能是缺血性HF的一种可转化模式。
CD4+ T-cells facilitate wound healing post-myocardial infarction (MI) but promote left-ventricular (LV) remodeling during ischemic heart failure (HF; 8 weeks post-MI). Therefore, it is critical to understand if sustained CD4+ T-cell activation leads to this pathological response, or if phenotypically different T-cells are activated during MI vs. HF. Using flow cytometry, we found that cardiac CD4+ T-cells exhibit two distinct patterns of transmigration. First pattern consisted of a rapid CD4+ T-cell response with maximal levels seen at 3 days post-MI which return to baseline by 14 days. However, during HF we observed a 2nd phase of activation and CD4+ T-cells were ∼20-fold higher in HF as compared to sham-operated mice. Importantly, these biphasic kinetics were observed with all major T-cell subsets such as Th1, Th2, Th17, and regulatory T-cells suggesting a global change. To determine the role of this 2nd peak of T-cell activation, CD4-iDTR mice were generated and treated with DT every 10 from 28 days post-MI to deplete CD4+ T-cells during chronic HF. While littermate control mice showed increased end-systolic and end-diastolic volumes (ESV and EDV) and decreased ejection fraction (EF) from 4 to 8 weeks post-MI, depletion of CD4+ T-cells in Cre + mice significantly blunted LV remodeling and inhibited progressive increases in the EDV and ESV, and reduction in EF. This suggests that CD4+ T-cell responses occurring during HF are different than those occurring during MI and promote LV remodeling and progressive cardiac dysfunction. Temporal immunomodulation of CD4+ T-cells could be a translatable modality for ischemic HF.
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DOI：
10.1161/circheartfailure.115.002225
发表时间：
2015-07
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Nevers T;Salvador AM;Grodecki-Pena A;Knapp A;Velázquez F;Aronovitz M;Kapur NK;Karas RH;Blanton RM;Alcaide P
通讯作者：
Alcaide P
影响因子：
37.8
作者：
Ngwenyama N;Kirabo A;Aronovitz M;Velázquez F;Carrillo-Salinas F;Salvador AM;Nevers T;Amarnath V;Tai A;Blanton RM;Harrison DG;Alcaide P
通讯作者：
Alcaide P
影响因子：
15.9
作者：
Rieckmann, Max;Delgobo, Murilo;Ramos, Gustavo Campos
通讯作者：
Ramos, Gustavo Campos
DOI：
10.1152/ajpheart.00137.2019
发表时间：
2019-09-01
影响因子：
4.8
作者：
Covarrubias, Roman;Ismahil, Mohamed Ameen;Bansal, Shyam S.
通讯作者：
Bansal, Shyam S.
影响因子：
37.8
作者：
Hofmann, Ulrich;Beyersdorf, Niklas;Frantz, Stefan
通讯作者：
Frantz, Stefan