Bruno Roxana, Sabater Lidia, Sospedra Mireia, Ferrer-Francesch Xavier, Escudero Domingo, Martínez-Cáceres Eva, Pujol-Borrell Ricardo
Laboratory of Immunobiology for Research and Diagnostic Applications (LIRAD) Transfusion Center and Tissue Bank, Hospital Universitari Germans Trias i Pujol, Carretera de Canyet s/n, E-08916 Badalona, Barcelona, Spain.
Eur J Immunol. 2002 Oct;32(10):2737-47. doi: 10.1002/1521-4141(2002010)32:10<2737::AID-IMMU2737>3.0.CO;2-0.
An important feature of central nervous system (CNS) immune privilege is that antigens expressed in CNS are sequestered and not available for central tolerance induction. Tissue distribution and, more specifically, thymic expression of many of the CNS putative autoantigens have not yet been clearly established in humans. We have addressed this question for the putative multiple sclerosis(MS) autoantigens alphaB-crystallin, S100beta, proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG)-alpha and MOG-beta isoforms, using quantitative RT-PCR on human thymus (total, cell fractions and microdissected specimen) and on a panel of peripheral tissues. alphaB-crystallin, S100beta and the DM20 isoform of PLP were clearly expressed in the thymus and also in selected peripheral tissues. In contrast, the expression of MOG out of the CNS was not observed. Within the human thymus, the level of CNS antigen expression was found higher in the stromal epithelial enriched cell fraction, and in microdissected samples of the medullary compartment. These results indicate that most of the antigens involved in MS are expressed in the thymus, suggesting a possible role in central tolerance. However, MOG and, to a lesser extent PLP, conform the classical concept of sequestered antigens, thus supporting the involvement of MOG in autoimmune demyelinating diseases.
中枢神经系统（CNS）免疫赦免的一个重要特征是，CNS中表达的抗原被隔离，无法用于诱导中枢耐受。许多CNS假定自身抗原的组织分布，尤其是胸腺表达，在人类中尚未明确确定。我们使用定量逆转录聚合酶链反应（RT-PCR）技术，对人类胸腺（整体、细胞组分和显微切割标本）以及一组外周组织进行检测，以研究假定的多发性硬化症（MS）自身抗原αB-晶状体蛋白、S100β、蛋白脂蛋白（PLP）和髓鞘少突胶质细胞糖蛋白（MOG）的α和β亚型。αB-晶状体蛋白、S100β和PLP的DM20亚型在胸腺以及某些外周组织中均有明显表达。相比之下，未观察到CNS外的MOG表达。在人类胸腺中，发现CNS抗原在富含基质上皮的细胞组分以及髓质区的显微切割样本中的表达水平更高。这些结果表明，大多数参与MS的抗原在胸腺中表达，提示其在中枢耐受中可能发挥作用。然而，MOG以及程度较轻的PLP符合隔离抗原的经典概念，从而支持MOG参与自身免疫性脱髓鞘疾病。
