Atherosclerosis.
Atherosclerosis.
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DOI：
10.1161/circresaha.118.313816
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发表时间：
2018-10-26
影响因子：
20.1
通讯作者：
Ley K
中科院分区：
文献类型：
--
作者：
Kobiyama K;Ley K
直到最近，没有直接证据表明ApoB表位特异性CD4 T细胞存在。为了解决这个问题，我们开发了MHC-II四聚体来检测人类和小鼠中的这种细胞。四聚体由4个携带抗原肽的重组MHC-II分子组成，并由荧光染料偶联链亲和素结合在一起。我们重点研究了ApoB表位P18，该表位在小鼠ApoB和人类ApoB中序列相同。P18结合小鼠MHC-II等位基因IA b和DRB1* 07: 01，约8%的人表达。为了检测apob特异性CD4+ T细胞，我们构建了人apob肽P18: DRB1* 07:01四聚体，发现在人外周血单核细胞中存在识别P18的CD4+ T细胞。这些p18特异性CD4+ T细胞在有和没有亚临床CVD的受试者中都有发现。有趣的是，大多数来自无CVD个体的p18特异性CD4+ T细胞表达FoxP3（叉头盒P3），这是Tregs的定义转录因子。然而，来自亚临床CVD患者的p18特异性CD4+ T细胞单独或与FoxP3一起表达th17定义转录因子r γτ（视黄酸受体相关孤儿受体γτ）或th1定义转录因子T-bet。这是人类外周血母细胞中存在自我肽识别CD4+ T细胞的第一个证据。在动脉粥样硬化的过程中，这些细胞的表型似乎发生了变化。
Until recently, there was no direct evidence that ApoB epitope-specific CD4 T cells exist. To address this question, we developed MHC-II tetramers to detect such cells in both humans and mice. A tetramer consists of 4 molecules of recombinant MHC-II loaded with the antigenic peptide and held together by fluorochrome-conjugated streptavidin. We focused on the ApoB epitope P18, which is sequenceidentical in mouse ApoB and human APOB. P18 binds the mouse MHC-II allele IA b and DRB1* 07: 01 expressed by≈ 8% of humans. To detect APOB-specific CD4+ T cells, we created human APOB-peptide P18: DRB1* 07: 01 tetramers and found that P18-recognizing CD4+ T cells exist in human PBMCs (peripheral blood mononuclear cells). These P18-specific CD4+ T cells were found in subjects with and without subclinical CVD. Interestingly, the majority of P18-specific CD4+ T cells from individuals without CVD expressed FoxP3 (forkhead box P3), the defining transcription factor of Tregs. However, P18-specific CD4+ T cells from subclinical CVD patients expressed the Th17-defining transcription factor RORγτ (retinoic acid receptor-related orphan receptor γτ) or the Th1-defining transcription factor T-bet alone or together with FoxP3. 9 This is the first evidence that self-peptide recognizing CD4+ T cells exist in human PBMCs. The phenotype of these cells seems to change during atherosclerosis progression.