Gamliel Adir, Werner Lael, Pinsker Marina, Salamon Naomi, Weiss Batia, Shouval Dror S
Pediatric Gastroenterology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Clin Exp Gastroenterol. 2020 Oct 2;13:439-447. doi: 10.2147/CEG.S271565. eCollection 2020.
The integrin α4β7 is highly expressed on activated T cells and is thought to direct homing of lymphocytes to the intestine. Since ulcerative colitis (UC) and Crohn's disease (CD) are characterized by mucosal oligoclonal T cells' expansion, we aimed to assess whether similar repertoire features are identified in circulating gut-specific memory T cells.
Memory CD3 T cells were isolated from blood samples of control subjects and patients with active UC or CD and then FACS-sorted into α4β7 and α4β7 populations. DNA was extracted from each subset and subjected to next-generation sequencing of the TCRβ. Different repertoire characteristics were compared between α4β7 and α4β7 subsets for each subject, and between groups.
The percentages of memory T cells and α4β7 cells were comparable between groups. α4β7 memory T cells displayed a polyclonal distribution, in control subjects and in UC or CD patients, with similar indices of diversity. Strikingly, the clonal overlap between α4β7 and α4β7 T cells for each subject in all three groups was high, ranging between 20%-50%. We were unable to identify shared T cell clones that were specific to one of the groups.
α4β7 memory T cells exhibited a polyclonal repertoire in both control subjects and patients with active inflammatory bowel disease, with high rates of overlap with α4β7 memory T cells. Our study, along with additional recent reports, may suggest that the suppression of intestinal inflammation by vedolizumab is independent of the drug's effect on T cell migration to the gut.
整合素α4β7在活化的T细胞上高度表达，被认为可引导淋巴细胞归巢至肠道。由于溃疡性结肠炎（UC）和克罗恩病（CD）的特征是黏膜寡克隆T细胞扩增，我们旨在评估在循环的肠道特异性记忆T细胞中是否能发现类似的谱系特征。
从对照受试者以及活动性UC或CD患者的血样中分离记忆性CD3 T细胞，然后通过荧光激活细胞分选术（FACS）分为α4β7阳性和α4β7阴性群体。从每个亚群中提取DNA，并进行TCRβ的下一代测序。比较每个受试者α4β7阳性和α4β7阴性亚群之间以及各群体之间不同的谱系特征。
各群体之间记忆T细胞和α4β7阳性细胞的百分比相当。在对照受试者以及UC或CD患者中，α4β7阳性记忆T细胞呈多克隆分布，具有相似的多样性指数。令人惊讶的是，所有三组中每个受试者的α4β7阳性和α4β7阴性T细胞之间的克隆重叠率都很高，在20%至50%之间。我们无法识别出特定于某一组的共享T细胞克隆。
在对照受试者和活动性炎症性肠病患者中，α4β7阳性记忆T细胞均表现出多克隆谱系，与α4β7阴性记忆T细胞的重叠率很高。我们的研究以及最近的其他报告可能表明，维多珠单抗对肠道炎症的抑制作用独立于该药物对T细胞迁移至肠道的影响。
