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B-Crystallin to T Cells in Active Multiple Sclerosis Lesions: An Early Event Following Inflammatory Demyelination1
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Division of Immunological and Infectious Diseases, TNO Prevention and Health, Leiden, The Netherlands;
Department of Cell Biology and Immunology, Faculty of Medicine, Free University, Amsterdam, The Netherlands; and
Department of Neurochemistry, Institute of Neurology, University College London, London, United Kingdom
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, 
B-crystallin has been shown to be an
important myelin Ag to human T cells. Since B-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, B-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
B-crystallin. The disappearance of B-crystallin from macrophages
even before MOG was confirmed by in vitro studies; within 6 h
after myelin-uptake B-crystallin disappears from the phagosomes.
B-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
B-crystallin-primed T cells in terms of proliferation and IFN-
secretion. In addition, B-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, B-crystallin
is available for functional presentation to T cells early during
inflammatory demyelination.
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