Print Email Facebook Twitter Presentation of αB-crystallin to T cells in active multiple sclerosis lesions: An early event following inflammatory demyelination Title Presentation of αB-crystallin to T cells in active multiple sclerosis lesions: An early event following inflammatory demyelination Author Bajramović, J.J. Plomp, A.C. van der Goes, A. Koevoets, C. Newcombe, J. Cuzner, M.L. van Noort, J.M. Publication year 2000 Abstract In the development of multiple sclerosis (MS), (re)activation of infiltrating T cells by myelin-derived Ags is considered to be a crucial step. Previously, αB-crystallin has been shown to be an important myelin Ag to human T cells. Since αB-crystallin is an intracellular heat shock protein, the question arises at what stage, if any, during lesional development in MS this Ag becomes available for CD4+ T cells. In 3 of 10 active MS lesions, αB-crystallin could be detected inside phagocytic vesicles of perivascular macrophages, colocalizing with myelin basic protein and myelin oligodendrocyte glycoprotein (MOG). Although the detectability of MOG in phagosomes is considered as a marker for very recent demyelination, MOG was detected in more macrophages and in more lesions than αB-crystallin. The disappearance of αB-crystallin from macrophages even before MOG was confirmed by in vitro studies; within 6 h after myelin-uptake αB-crystallin disappears from the phagosomes, αB-Crystallin-containing macrophages colocalized with infiltrating T cells and they were characterized by expression of MHC class II, CD40, and CD80. To examine functional presentation of myelin Ags to T cells, purified macrophages were pulsed in vitro with whole myelin membranes. These macrophages activated both myelin- primed and αB-crystallin-primed T cells in terms of proliferation and IFN-γ secretion. In addition, αB-crystallin-pulsed macrophages activated myelin- primed T cells to the same extent as myelin-pulsed macrophages, whereas myelin basic protein-pulsed macrophages triggered no response at all. These data indicate that, in active MS lesions, αB-crystallin is available for functional presentation to T cells early during inflammatory demyelination. Chemicals/CAS: Antigens, CD40; Antigens, CD80; Autoantigens; Cathepsins, EC 3.4.-; Crystallins; Histocompatibility Antigens Class II; Myelin Proteins Subject HealthAlpha crystallinB7 antigenBeta crystallinCD40 antigenCytokineGamma interferonMajor histocompatibility antigen class 2Myelin basic proteinAdultBlood brain barrierClinical articleControlled studDemyelinationHuman tissueImmunohistochemistryInflammationMacrophage functionMultiple sclerosisNeurologic diseaseAntigen PresentationAntigens, CD40Antigens, CD80AutoantigensCathepsinsCell MovementCrystallinsDemyelinating DiseasesHistocompatibility Antigens Class IIHumansHydrolysisInflammationMacrophagesMultiple SclerosisMyelin ProteinsMyelin SheathPhagocytosisT-Lymphocytes To reference this document use: http://resolver.tudelft.nl/uuid:083436cc-a88f-4d53-bb20-923ca15a4aae TNO identifier 235525 ISSN 0022-1767 Source Journal of Immunology, 164 (8), 4359-4366 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.