Donor Exosomes May Induce Immune Tolerance

Researchers seeking ways to prevent the body from rejecting transplanted organs without the need for drugs have found that exosomes from donor dendritic cells are a rich source of antigens that are readily incorporated by the host's immature dendritic cells and are expressed in a fashion that promotes tolerance in the host for that donor's organs.

Investigators at the University of Pittsburgh (PA, USA) worked with a mouse model to monitor the effect of donor exosomes on the host immune system. They injected dye-labeled exosomes extracted from dendritic cells of one mouse strain into the bloodstream of mice of a different strain. Antigen expression was followed using flow cytometry, confocal microscopy, and immuno-electron microscopy.

They found that the injected exosomes were rapidly internalized by one of three recipient immune system cell types: splenetic antigen-presenting dendritic cells, macrophages, and liver Kupffer cells. Of particular interest was the finding that the process of internalizing the donor exosomes did not affect maturation of the dendritic cells, and the mature dendritic cells expressed a mixture of host and donor antigens for presentation to CD4+ T cells. These findings were published in the November 15, 2004, issue of Blood.

"This finding is significant because current immunosuppression therapies used in the clinical setting are not able to efficiently prevent T cell activation via the indirect pathway. Perhaps the CD4+ T cells normally involved in this pathway would retreat from attack if they encountered a cell surface marker that is of both donor and recipient origin, such as that which we observed following the dendritic cell's internalization of the donor-derived exosomes,” said first author Dr. Adrian Morelli, a researcher in the transplantation institute at the University of Pittsburgh.



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