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Monitoring Stem Cell Research 
presentation. Indirect recognition of allo-HLA peptides is important 
for the initiation and spreading of the immune response to other 
epitopes within the allograft. So-called "spreading" of indirect T cell 
responses to other allo-HLA epitopes expressed by graft tissue is 
strongly predictive of recurring episodes of rejection. Tolerance 
induction to the dominant donor determinants represents potential 
effective strategy for blocking indirect alloresponses and ensuring 
long-term graft survival in cinimeil models. 
Tolerance Induction 
Advances in surgical methods and current immunosuppressive 
therapies have led to significant improvement in short-term graft 
survival, however long-term survival rates remain poor. For example, 
whereas both kidney and heart allografts have one-year graft 
survival rates of 85 to 95 percent, only about 50% of transplanted 
hearts survive five years and only about 50% of kidney grafts survive 
ten years. Thus, despite being able to achieve short-term success, 
these relatively poor long-term graft survival rates demonstrate the 
limitations of the current clinical immunosuppressive regimens to 
enable long-term immune evasion by the graft. Consequently, a 
major goal of transplantation immunobiologists is to induce donor- 
specific tolerance, allowing the long-term survival of human 
allografts vhthout the need of HLA-compatibility and without the 
continuous recipient immunosupression leading to the concomitant 
risks of infection, malignancy, and/or other specific drug side effects. 
This would theoretically improve long-term graft survival, reduce or 
eliminate the continuing need for expensive, toxic and non-specific 
immunosuppressive therapy and enhance the quality of life. 
Insight into some of the mechanisms involved in tolerance 
induction has been gained from pre-clinical and clinical studies in 
numerous animal models and in patients, particularly those with liver 
allografts which typically do not induce a prominent immune 
response leading to rejection. One possible mechanism by which 
liver transplantation results in allograft tolerance tolerance may be 
that the donor or "passenger" lymphoid cells in the transplanted liver 
emigrate and take up residence in the recipient's immune organs, 
such as the thymus or lymph nodes. Donor lymphocytes at these 
sites might "re-educate" the recipient immune system so that the 
donor organ is not recognized as foreign. In an attempt to initiate a 
similar process in other organ recipients, transfusions of donor blood 
or bone marrow have been used to enhance solid organ graft survival 
in animal models and in clinical trials. These studies are currently 
ongoing in various organ systems. 
PRE -PUBLICATION VERSION 
