Martino G, Clementi E, Brambilla E, Moiola L, Comi G, Meldolesi J, Grimaldi L M
Neuroimmunology Unit, University of Milan, San Rafaele Scientific Institute, Italy.
Proc Natl Acad Sci U S A. 1994 May 24;91(11):4825-9. doi: 10.1073/pnas.91.11.4825.
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. The etiology of the disease is still unknown. Activated T lymphocytes are considered essential in mediating the inflammatory process leading to demyelination in MS. They operate through a complex network of cytokines among which gamma interferon (gamma-IFN) plays a key role. Here we report that exposure to gamma-IFN of T lymphocytes from patients with MS activates, by a protein kinase C-mediated pathway, a previously undescribed gamma-IFN-activated Ca2+ influx, functionally coupled to the gamma-IFN receptor. The influx mainly expressed by CD4+ T lymphocytes, was found in 12 of 15 (80%) patients with clinically active MS and in 14 of 30 (46%) patients with stable MS. The influx was found in only 3 of 24 (12%) control patients and in none of the 15 healthy subjects studied. Our results document the appearance in MS lymphocytes of a gamma-IFN-activated, protein kinase C-dependent, Ca2+ influx that might be due to the expression of a new cation-specific plasmalemma channel. This finding suggests that at least part of gamma-IFN's contribution to the pathogenesis of MS is exerted through a Ca(2+)-dependent regulation of T lymphocyte activity.
多发性硬化症（MS）是一种中枢神经系统的免疫介导性脱髓鞘疾病。该疾病的病因仍不清楚。活化的T淋巴细胞被认为在介导导致MS脱髓鞘的炎症过程中至关重要。它们通过复杂的细胞因子网络发挥作用，其中γ干扰素（γ-IFN）起关键作用。在此我们报告，来自MS患者的T淋巴细胞暴露于γ-IFN后，通过蛋白激酶C介导的途径激活了一种先前未描述的γ-IFN激活的Ca2+内流，其在功能上与γ-IFN受体偶联。这种内流主要由CD4+T淋巴细胞表达，在15例临床活动期MS患者中的12例（80%）以及30例稳定期MS患者中的14例（46%）中被发现。在24例对照患者中仅3例（12%）发现了这种内流，而在所研究的15名健康受试者中均未发现。我们的结果证明了在MS淋巴细胞中出现了一种γ-IFN激活的、蛋白激酶C依赖性的Ca2+内流，这可能是由于一种新的阳离子特异性质膜通道的表达所致。这一发现表明，γ-IFN对MS发病机制的贡献至少部分是通过对T淋巴细胞活性的Ca(2+)依赖性调节来实现的。
