October 1, 2015

Tolerating a transplant

A new genetic model has generated new strategies for promoting tolerance to transplants – and improving long-term transplant outcomes – in the background of autoimmune disease.

Patients with autoimmune diseases, such as lupus and type 1 diabetes, resist immune tolerance – a state of unresponsiveness of the immune system, which could be harnessed to promote permanent survival of organ transplants. Because these patients are common transplant recipients, understanding how they resist tolerance is important for improving long-term transplant outcomes.

To investigate immune tolerance in the background of autoimmune disease, Daniel Moore, M.D., Ph.D., and colleagues studied transplantation in a mouse model of lupus.

They report in the American Journal of Transplantation that lupus-prone mice resist immune regulation by CD4 and CD8 T regulatory cells, leading to deleterious expansion of immune system T and B effector cells. They further demonstrated that lupus-prone mice resist induction of immune tolerance to transplanted pancreatic islets, even though the mice do not have pre-existing immune reactivity to the pancreas.

The findings provide a new genetic model for studying resistance to transplant tolerance in autoimmunity and suggest new strategies for promoting transplant tolerance.

This research was supported by National Institutes of Health grants DK090146, DK097410, HL088364, GM007347 and by a Juvenile Diabetes Research Foundation Career Development Award.

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