Presentation of alpha B-crystallin to T cells in active multiple sclerosislesions: An early event following inflammatory demyelination

In the development of multiple sclerosis (MS), (re)activation of infiltrati ng T cells by myelin-derived Ags is considered to be a crucial step, Previo usly, alpha B-crystallin has been shown to be an important myelin Ag to hum an T cells. Since alpha 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 lesi ons, alpha B-crystallin could be detected inside phagocytic vesicles of per ivascular macrophages, colocalizing with myelin basic protein and myelin ol igodendrocyte glycoprotein (MOG), Although the detectability of MOG in phag osomes is considered as a marker for very recent demyelination, MOG was det ected in more macrophages and in more lesions than alpha B-crystallin. The disappearance of alpha B-crystallin from macrophages even before MOG was co nfirmed by in vitro studies; within 6 h after myelin-uptake alpha B-crystal lin disappears from the phagosomes. alpha B-Crystallin-containing macrophag es colocalized with infiltrating T cells and they were characterized by exp ression of MHC class II, CD40, and CD80, To examine functional presentation of myelin Ags to T cells, purified macrophages were pulsed in vitro with w hole myelin membranes. These macrophages activated both myelin-primed and a lpha B-crystallin-primed T cells in terms of proliferation and IFN-gamma se cretion, In addition, alpha B-crystallin-pulsed macrophages activated myeli n-primed T cells to the same extent as myelin-pulsed macrophages, whereas m yelin basic protein-pulsed macrophages triggered no response at all. These data indicate that, in active MS lesions, alpha B-crystallin is available f or functional presentation to T cells early during inflammatory demyelinati on.