The latter condition is obtained by myeloablation and immunosuppression, followed by stem cell transplantation MEK162 ARRY-438162 (SCT) [2]. The former mode of tolerance induction is seen in patients with severe combined immunodeficiency disease (SCID) treated with SCT [3] or in fetal patients subjected to SCT prior to their immunological maturation [4]. We review herein our results in infants and human fetuses who were treated by fetal liver SCT and who developed full tolerance to both donor and host antigens [5�C13]. 2. Patients, Materials, and Methods Nineteen patients with SCID, including 17 infants and 2 fetuses, received fetal liver SCT [4, 7]. Fetal livers were obtained from dead human fetuses under Inhibitors,Modulators,Libraries conditions approved by the French National Committee for Bioethics. Donors Inhibitors,Modulators,Libraries were aged less than 14 weeks after fertilization.

A cell suspension was prepared, cell viability was checked, and cells were administered by intravenous or intraperitoneal Inhibitors,Modulators,Libraries injection. In the two fetal recipients with SCID, the cells were injected into the umbilical vein in utero [4]. Fourteen of the 19 patients had evidence of donor cell engraftment and developed immunological reconstitution. All were subjected to immunological investigations, especially on peripheral blood lymphocytes (PBLs). The studies reported herein mainly concern three children who were analyzed more extensively over a long period of time (21�C34 years). Three nonimmunodeficient fetuses with various diseases (thalassemia major, Niemann-Pick type A disease and hemophilia A) were also analyzed for at least 2 years after the in utero SCT (which was performed by the intraperitoneal route).

HLA typing was initially carried out on PBL, T-cell clones, and EBV-transformed B-cell lines using a previously described cytotoxicity assay [14] and was confirmed more recently using molecular biological methods. To analyze responses in mixed leukocyte cultures (MLCs), PBL from the patients were cultured together with a variety of irradiated stimulator Inhibitors,Modulators,Libraries cells. The proliferative response of T lymphocytes to these stimulator cells was determined by the degree of tritiated thymidine incorporation [12]. Inhibitors,Modulators,Libraries The experiments were performed in triplicate, and the results are expressed as the mean �� standard deviation (SD). 3. Results 3.1. HLA Typing Table Brefeldin_A 1 summarizes the HLA phenotypes (class I and class II) of cells of donor and host origin that were prepared from the three most extensively studied patients, all of whom have had a stable chimerism for many years. They had received fetal liver SCTs from several donors but only the HLA phenotype of the permanently engrafted cells is reported here. Table 1 HLA phenotypes of host cells and of cells of donor origin found in three chimeric patients.