Human islet transplantation is limited, in part, due to the lack of an abundant supply of donated human islets. Islets from other animals, such as specially-bred pigs, may help overcome this limitation. However, transplanting beta cells from another animal into humans increases the potential for a rejection reaction, adding another challenge to using such an approach for restoring lost insulin production in a person with T1D. The authors investigated whether pig islets modified to produce anti-human CD2 antibodies would protect them from immune attack when transplanted to a “humanized” mouse. Three versions of the anti-CD2 antibodies were prepared for testing. All 3 forms of the tested anti-CD2 antibody bound human T cells in the lab and all 3 anti-CD2 antibodies could deplete human CD3(+) T cells in a humanized mouse. Humanized mice transplanted with islets containing one version of the anti-CD2 antibody preparation afforded depletion of CD3(+) T cells at the transplant site leaving the systemic immune system intact. The investigators concluded that grafted pig islets engineered to locally produce a single antibody against T cells may reduce the need for conventional, systemic immunosuppression during pig islet transplantation in individuals with T1D.
Ramifications for Individuals with T1D:
Islet transplantation triggers normal rejection responses by the human immune system. Modulating the local immune environment is a promising approach to allow long term islet survival and function without the use of chronic systemic immunosuppression following an islet transplant. This study lends further support to developing this approach to overcome some hurdles experienced during such transplants.
This study was funded in part by JDRF.
Investigators and Institutions:
This study was conducted by Drs. Philip O’Connell, Andrew Lew and their colleagues at the University of Sydney and University of Melbourne in Australia.
Brady JL, Sutherland RM, and others. Anti-CD2 producing pig xenografts effect localized depletion of human T cells in a huSCID model. Xenotransplantation. 2013 Mar-Apr;20(2):100-9. Doi: 10.1111/XEN.12025. Epub 2013 Feb 27.