Ex vivo expanded Treg cells protection against allograft rejection

Chicago, IL, USA -

Understanding methods of manipulating the immune system to accept allogeneic grafts without the continued need for immune suppression would not only solve the problem of organ transplant rejection but would also bring stem cell therapy (especially embryonic) closer to reality. One interesting method of bringing about such an "immunological tolerance" is through the upregulation of activity of T regulatory cells. Previously it has been demonstrated that in some model systems, T regulatory cells contribute to the initiation and maintenance of the state of immunological tolerance in part through their self-perpetuating tolerogenic loop with dendritic cells.

In a recent study (Xia et al. Ex vivo-expanded natural CD4+CD25+ regulatory T cells synergize with host T-cell depletion to promote long-term survival of allografts. Am J Transplant. 2008 Feb;8(2):298-306) the question of therapeutic utilization of T regulatory cells was asked in an animal model of heart transplantation.

Treg cells were generated by culturing recipient strain CD4+ CD25+ cells with Dynabeads that co-expressed antibodies to CD3 and CD28 in the presence of donor dendritic cells, IL-2, and TGF-beta. The generated Tregs were capable of extending allograft survival in a donor specific manner.

These data support the feasibility of ex vivo expansion of CD4+ CD25+ Treg cells and their use in animal models. It will be interesting to see whether adoptive Treg therapies will be used in conjunction with approaches that increase Treg activity and/or number in vivo such as administration of IVIG, rapamycin, and RANK-ligand.