(视频来源:MedPage Today)
来自美国拉赫拉过敏与免疫研究所的一组研究人员通过使用高科技成像技术,观察到了小鼠胰腺内自身免疫性T淋巴细胞攻击产生胰岛素的胰岛B细胞的过程,改发现在揭示I型糖尿病的发病机理中具有重大意义,其研究结果近日被发表在《临床研究杂志》(Journal of Clinical Investigation)上。
I型糖尿病是一种自身免疫性疾病,又称胰岛素依赖性糖尿病,发病人群年龄较小,其发病机理是感染(尤其是病毒感染)、毒物等因素诱发机体产生异常自身体液和细胞免疫应答,导致胰岛β细胞损伤,胰岛素分泌减少,多数患者体内可检出抗胰岛β细胞抗体,通常需使用胰岛素进行治疗。
研究人员发现,T细胞一开始在胰腺内漫无目的地随机运动,当其捕获到胰岛B细胞时,便释放毒性介质,数小时即可杀死胰岛B细胞。
研究者还发现了T细胞进入胰腺的特定血管,人们或许可以通过该途径阻止T细胞进入胰腺,从而达到治疗I型糖尿病的目的。
研究者指出,要使小鼠发展成为I型糖尿病,需要其体内数以千万计的T淋巴细胞来破坏大量的胰岛B细胞,这也解释了I型糖尿病的临床前期阶段较长。(生物谷bioon.com)
doi:10.1172/JCI59285
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Intravital imaging of CTLs killing islet cells in diabetic mice
Ken Coppieters, Natalie Amirian and Matthias von Herrath.
Type 1 diabetes (T1D) is caused by autoimmune destruction of the insulin-producing β cells in the pancreatic islets, which are essentially mini-organs embedded in exocrine tissue. CTLs are considered to have a predominant role in the autoimmune destruction underlying T1D. Visualization of CTL-mediated killing of β cells would provide new insight into the pathogenesis of T1D, but has been technically challenging to achieve. Here, we report our use of intravital 2-photon imaging in mice to visualize the dynamic behavior of a virally expanded, diabetogenic CTL population in the pancreas at cellular resolution. Following vascular arrest and extravasation, CTLs adopted a random motility pattern throughout the compact exocrine tissue and displayed unimpeded yet nonlinear migration between anatomically nearby islets. Upon antigen encounter within islets, a confined motility pattern was acquired that allowed the CTLs to scan the target cell surface. A minority of infiltrating CTLs subsequently arrested at the β cell junction, while duration of stable CTL–target cell contact was on the order of hours. Slow-rate killing occurred in the sustained local presence of substantial numbers of effector cells. Collectively, these data portray the kinetics of CTL homing to and between antigenic target sites as a stochastic process at the sub-organ level and argue against a dominant influence of chemotactic gradients.