Side-effect of radiation treatment offers new hope for preventing transplant rejection

Radiation treatment causes changes in immune system which encourage body to accept donated bone marrow - News Release

Imperial College London News Release

Under strict embargo for 22.00 BST / 17.00 EST
Monday 7 May 2007

A radiation treatment currently used to prepare patients for a bone marrow transplant causes changes in the immune system which encourage the body to accept donated bone marrow rather than reject it, according to new research.

The scientists, from Imperial College London, hope that their findings will help the development of new therapies to stop the immune system from rejecting these and other kinds of transplants. The research, which was funded by Cancer Research UK, is published today in the journal PNAS.

Bone marrow transplants are used to enable patients to produce healthy blood cells. However, the host immune system can sometimes attack the donor immune cells from the transplanted bone marrow. Radiation treatment is given before the transplant to create space in the host bone marrow for donor immune cells to inhabit and, in the case of patients with leukaemia, to kill the leukaemia cells.

The new research, which used mouse models, shows that during this process, many of the T cells which mediate the immune response are killed. However, regulatory T cells are able to survive and proliferate, suggesting that they have more resistance to irradiation. Regulatory T cells stop other T cells from attacking the transplanted cells, and so encourage the immune system to accept the transplant.

At present this effect is not sufficiently strong to prevent rejection of bone marrow transplants, but the scientists hope the findings will enable them to develop new ways of curbing rejection.

Professor Francesco Dazzi , from the Kennedy Institute of Rheumatology at Imperial College London, who led the study, said: "Perfect tissue matching is rarely possible and this means the body's immune system recognises transplanted bone marrow as foreign and attacks it. Our new research shows that the regulatory cells which proliferate are able to recognise the foreign tissue and yet stop other immune cells from attacking it. Having uncovered a fundamental process the body uses to control the response to foreign tissue, we can now develop strategies to exploit this effect and control rejection of bone marrow and potentially other organ transplants."

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Notes to editors:

1. “Low-intensity transplant regimens facilitate recruitment of donor-specific regulatory T cells that promote hematopoietic engraftment” Proceedings of the National Academy of Sciences, 7 May 2007

Ling Weng*, Julian Dyson†, and Francesco Dazzi*‡

Departments of *Haematology and †Immunology, Stem Cell Biology Section, Imperial College London

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