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The immune processes involved in transplant rejection depend on the type of
tissue or organ, and whether the donor and recipient belong to the same or
different species. The shortage of human donor organs/tissues for
transplantation in the clinic has led many researchers to consider the use of
animal tissues and organs. The process of transplantation between different
species is called xenotransplantation. One major concern has been the possible
transfer of animal viruses to humans (xenozoonosis).
The size and make-up of organs / tissues from pigs and humans are similar and
this has led to pigs being chosen as the preferred donor animal species for
transplantation to humans. Pig tissues, however, normally produce their own
virus called porcine endogenous retrovirus (PERV). This virus does not damage
the pig cells and both the host and virus live happily together. While
laboratory experiments have shown that this virus can be transferred to human
cells, there has been no evidence for such transfer in patients who, for
example, have been treated with pig skin for serious burns.
Various proteins on the surface of tissue cells help identify a tissue
transplant as foreign and they act as targets (like a bullseye) for
destruction by the bodys immune cells. With human-to-human transplants such
proteins are encoded by a group of genes called the major histocompatibility
complex (MHC). Studies by others have shown that a different marker (a special
sugar) is recognised on the blood vessels in pig organs. Our studies of pig
tissue transplants (lacking donor blood vessels) in mice have identified yet
another important marker. This new marker (protein) comes from the porcine
endogenous retrovirus and is found on the surface of most pig cells. In mice
these pig viral proteins appear to be recognised in a similar way to pig MHC
proteins.
Other studies in our laboratory have indicated that if human cells were
infected by porcine endogenous retrovirus, such foreign viral proteins would be
recognised by the immune system and the infected cells would be eliminated. This
may explain why patients treated with pig tissues have not shown evidence of
infection. If, however, the normal immune response was weakened by strong drug
therapy, the infected cells harbouring pig virus would survive and this
situation could cause other health concerns.
We propose that problems associated with virus transfer following clinical
xenotransplantation could be avoided by not using strong immunosuppressive drugs
to prevent transplant rejection and/or by developing a special breed of pigs
which are unable to make endogenous retrovirus. A major aim of our research is
to develop safe procedures for preventing the rejection of tissue transplants
(such as pancreatic islets for treating Type 1 diabetes); such approaches would
eliminate the need for harmful immunosuppressive drugs. Research Highlights
an immune response against Porcine endogenous retrovirus (PERV)-specific
proteins accelerates the rejection of pig tissue or cell xenografts in mice
an immune response to PERV proteins can be more effective than an immune
response to pig MHC in inducing xenograft rejection
recognition of PERV proteins alone (in the absence of pig MHC) is sufficient
target for the rejection of pig cell xenografts PERV is a source of major
xenoantigens recognised during the rejection of pig tissue or cell xenografts | 
