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Tiny exosomes extracted from donor cells may be 'magic bullet' for drug-free transplants

nt dendritic cells and processed in a manner important for cell-surface recognition. What this means is that we can efficiently deliver donor antigen using the exosomes as our magic bullet. Further research will determine if we can actually influence transplant tolerance," explained Dr. Morelli, assistant professor of surgery at the University of Pittsburgh School of Medicine.

The function and mechanisms for dendritic cell-derived exosomes had never before been elucidated, so Dr. Morelli and colleagues sought to do so by following the fate of exosomes that they extracted from dendritic cells of one mouse strain and injected into the bloodstream of mice of a different strain. The exosomes were labeled with a dye, and methods such as flow cytometry, confocal microscopy and immuno-electron microscopy helped the researchers track their every movement and activity within the mouse.

Very quickly and efficiently, the donor exosomes were captured by one of three recipient immune system cell types: antigen-presenting dendritic cells and macrophages, both originating in the spleen, and Kupffer cells of the liver.

Of particular interest to the researchers were those exosomes that were caught by the dendritic cells of the spleen, the site where dendritic cells typically present antigens as bounty to T cells that do their part to destroy the foreign invaders. Yet, what the researchers discovered was that these dendritic cells internalized the exosomes instead of displaying them to T cells, this despite the exosomes' rich endowment of donor MHC molecules.

Once internalized, the exosomes were ushered inside larger vesicles, special endosomes called MHC-II enriched compartments, where they were processed with the dendritic cell's own MHC molecules. This hybrid MHC-II molecule, now loaded with a peptide of donor MHC, was then expressed on the cell's surface. As one family of MHC molecules, MHC-II serves as a beacon for a specific population of
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10-Nov-2004


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