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Regulatory cells comprise a highly heterogeneous T-cell population. It is assumed they are generated both in the thymus and periphery. According to some immunologists, any T-cell population has the potential to differentiate into cells with regulatory properties in the periphery. Following the discovery of their role in maintaining T-cell homeostasis and their ability to prevent autoimmune disease, allergy, and other types of hypersensitivity, regulatory cells have been the focus of intense studies over the last decade. During pregnancy, regulatory cells are believed to mediate tolerance to the fetus. In the unnatural event of transplantation, regulatory cells induce and maintain tolerance to the transplanted tissues or cells and prevent graft-versus-host disease. At the same time, however, regulatory cells are responsible for decreased immunity against tumors and infections. The data which have emerged to date concerning regulatory cells have not allow them to be definitively identified nor their characteristics to be clearly defined. This may be due to the existence of various regulatory cell populations as well as different modes of action depending on the experimental model. Contradictory in vitro and in vivo results and lack of certainty as to how the results of animal trials correspond with the human model are why the notion of harnessing regulatory cells as therapeutic agents is still a distant one, although raising great hopes. The aim of the following article is to make sense of the patchwork of available data concerning regulatory cells and review the potential use of these cells in the field of transplantation.

Children with severe combined immunodeficiency (SCID) die within 2 years of age if untreated. The only effective treatment for SCID since 1968 is a hematopoetic stem cells (HSC) transplantation. Only 25% of patients have an HLA matched related donor, while the rest have to be transplanted with T cells depleted haploidentical parental bone marrow, unrelated bone marrow or unrelated umbilical cord blood. In many cases, however, despite a positive outcome, children are not achieving B cell reconstitution and require regular IV Ig infusion. Gene therapy with genetically modified autologous cells offers a cure with no immunological complications such as graft rejection, graft versus host disease (GVHD) or post-transplantation immunosuppressive therapy. The first gene therapy trials were introduced in 1990 for adenosine deaminase (ADA) deficient patients who had failed to respond to PEG-ADA. Since then, three clinical trials have evaluated the transplantation of ex-vivo transduced autologous haematopoietic stem cells (HSC) to treat ADA deficiency. One trial used only bone marrow HSC, a second used bone marrow plus peripheral blood T lymphocytes, and a third used umbilical cord blood HSC. These trials give promise but also define the present limitations of gene therapy. Future protocols might be adjusted according to the new observations that ADA-expressing T cells have a strong selective advantage over ADA-deficient T cells. PEG-ADA enzyme therapy might be therefore contraindicated. Another new strategy might involve moderate conditioning prior to the reinfusion of genetically modified CD34+ cells, "making space" for transplanted HSC. The first successful gene therapy was reported for treatment of X-linked severe combined immunodeficiency (SCID-X1) in Science 2000. Since then, the group at the Hopital Necker in Paris has treated 11 patients with ex-vivo gene therapy for the deficiency of the common g chain. All eleven boys are alive, however, one of them recently developed a leukaemia-like disease. This case is being investigated to determine whether the genetic manipulations of the patient's HSC could be the reason for mutagenesis and how other factors could have contributed to this unfortunate event.