Regulatory T cells keep graft-versus-host disease in check

Bone marrow transplantation offers the hope of a complete cure for patients suffering from certain forms of cancer, such as leukemia or other immune deficiency diseases.

However, there is a risk that transplanted cells may recognize the recipient patient’s tissues as foreign and begin to attack them. This reaction, known as graft-versus-host disease (GVHD), can be lethal if it continues unchecked.

It has recently been shown in mice that the use of large numbers of immunoregulatory CD4+CD25+ T cells can induce tolerance to donor tissue following allogeneic hematopoietic stem cell transplantation and therefore control the development of GVHD.

The challenge however has been to obtain enough freshly purified CD4+CD25+ regulatory T cells from a single donor patient to achieve this therapeutic effect in a clinical setting.

In the December 4 issue of the Journal of Clinical Investigation José Cohen and colleagues from Centre National de la Recherche Scientifique in Paris describe a protocol to circumvent this difficulty.

The authors performed regulatory T cell expansion ex vivo by stimulation with allogeneic antigen-presenting cells, which has the additional effect of producing alloantigen-specific regulatory T cells. Regulatory T cells specific for recipient-type alloantigens, but not irrelevant regulatory T cells, controlled GVHD while favoring immune reconstitution.

Preferential survival of specific regulatory T cells was observed in the grafted animals. The results will be extremely useful in the design of future clinical trials that rely on the use of CD4+CD25+ regulatory T cells to control GVHD.

TITLE: Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia.

AUTHOR CONTACT:
José L. Cohen
Centre National de la Recherche Scientifique, Paris, France.
Phone: 33-1-42-17-74-61
Fax: 33-1-42-17-74-62
E-mail: jose.cohen@chups.jussieu.fr