NORMALIZATION OF THE PERIPHERAL-BLOOD T-CELL RECEPTOR V-BETA REPERTOIRE AFTER CULTURED POSTNATAL HUMAN THYMIC TRANSPLANTATION IN DIGEORGE-SYNDROME

Complete DiGeorge syndrome is an immunodeficiency disease characterize d by thymic aplasia and the absence of functioning peripheral T cells. A patient with this syndrome was transplanted with cultured postnatal human thymic tissue. Within 5 weeks of transplantation, flow cytometr y, T cell receptor V beta sequence analysis, and cell function studies showed the presence of oligoclonal populations of nonfunctional clona lly expanded peripheral T cells that were derived from pretransplantat ion T cells present in the skin. However, at 3 months posttransplantat ion, a biopsy of the transplanted thymus showed normal intrathymic T c ell maturation of host T cells with normal TCR V beta expression on th ymocytes. By 9 months posttransplantation, peripheral T cell function was restored and the TCR V beta repertoire became polyclonal, coincide nt with the appearance of normal T cell function. These data suggest t hat the transplanted thymus was responsible for the establishment of a new T cell repertoire via thymopoiesis in the chimeric thymic graft.