Research Group

  • Dr. Sean O’Herrin, Principal Investigator
  • Dr. Kenneth A. Newell, Collaborator
  • Dr. Jeffrey A. Bluestone, Collaborator

Location

  • University of Chicago, Chicago, USA

Title

  • Utilization of Immune System Molecules to Prolong Survival of Transplants

Illnesses such as kidney failure, diabetes and liver disease have a devastating effect on public health. For such diseases (and for a range of other diseases), the accepted treatment is organ transplantation.

Over the past decade, there has been remarkable progress in organ transplantation, and it is now the treatment of choice for the failure of organs such as the pancreas or kidney. In many cases, however, the benefit of transplantation may be short-lived. In fact, nearly one-third of all patients on waiting lists for donor organs have had their previous transplant fail. The failure of a transplanted organ is almost always due to a process called rejection.

The rejection of a tissue or organ transplant occurs because our white blood cells (or T cells) in our immune system are trained to protect us from foreign invaders. A special molecule found on virtually every cell, known as MHC, tells the T cell if foreign material from say, a viral or microbial invasion is present. Transplanted tissues, unless they are procured from an identical twin, are recognized as foreign, and are consequently attacked by "activated" T cells that have been targeted to the transplant, eventually damaging or destroying the graft.

It may now be possible to prevent this process by destroying or inactivating these activated T cells. However, care must be taken not to destroy the other "good" T cells that maintain protection against bacteria, viruses, etc. We have designed a series of custom MHC molecules that mimic transplanted tissues. The activated T cells, believing these molecules to be the transplanted tissue cells, lock on the MHC. Since these MHC molecules are not on a cell surface, but essentially out of context, they trick the T cells into a state of inactivation. Our "pepMHC" combinations will be tested in animals receiving organ transplants in order to test their effectiveness in preventing transplant rejection.