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

T cells called CD4+ T cells. Such cells are activated during chronic rejection in a process associated with the indirect pathway of immune recognition.

"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 Dr. Morelli.

Also significant, the researchers report, was that the process of internalizing the donor exosomes did not affect maturation of the dendritic cell. Only immature dendritic cells can capture antigens efficiently and are believed to participate in the induction of transplant tolerance. By contrast, once mature, dendritic cells are capable of triggering the T cell activation that leads to transplant rejection.

Additional research will be required to determine whether donor-derived exosomes will enhance the likelihood that an organ transplant from the same donor will be accepted. Under a recently awarded National Institutes of Health grant, Dr. Morelli plans to address this question with studies involving mice that receive heart transplants following infusion with exosomes from the same donor. A recent French study in rats, while offering no clues as to why, suggests the approach will be successful. In addition, animal studies conducted at Pitt by Paul Robbins, Ph.D., professor of molecular genetics and biochemistry, provide evidence that exosomes can reverse arthritis. Drs. Morelli and Robbins plan to collaborate in future research.

"This is an exciting new area of investigation, which appears to hold great promise in the area of transplant tolerance. So much more remains to be understood, but this current stud
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10-Nov-2004


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