Multiple sclerosis candidate autoantigens except myelin oligodendrocyte glycoprotein are transcribed in human thymus.

Abstract

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.