Studies on Immunologic Reconstitution after HLA-haplotype Mismatched parental Marrow Transplantation

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A. T cell-depletd, HLA-haplotype mismatched, parental marrow has been usedfor transplant in patients with severe immune deficiency diseases and leukemia. Previously, we succeeded in transplantation of soy bean agglutinin- and sheep red cell rosiesting-fractionated, maternal marrow in apatient with severe combined imunodeficiency (SIDC). Kinetics of immune reconstitution after the bone marrow transplantation (BMT) were investigated in this patient. 1. Cellular immunity recovered relatively rapidly with normal T cell subpopulations and positive delayedtype hyper sensitivity against PPD. Four years later, CD4^+ cells decreased and the ratio of CD4^+/CD8^+ was less than 1.0. Unusual T cells which express CD3 but neither CD4 nor CD8 antigens increased comprising 10 30 % of peripheral T cells. These CD3^+4^-8^SD1 cells, although not identified yet, seemed to correspond to cells which express the <gamma> protein of the T cell receptor but not its <alpha>- and <beta>- chains in association with the CD3 complex. 2. T cells in the patients were shown to be of donor origin but B cells to be of host origin. The reconstitution of humoral immunity was achieved 5 years after BMT, resulting in discontinuation of immunoglobulin replacement. This indicates that HLA haploidentical donor stem cells are able to differentiate and mature to functional T cells which can cooperate with host B cells for antibody production. 3. Little NK actiivty has been demonstrated during the course after BNT in the patient. Leu 7 cells were found soon after engraftment but Leu 11 cells in appeared first 5 years later.B. Last 2 years, two other patients underwent HLA-mismatched BMT; One with SCID succumbed to severe infection after the treatemnu and the other with Fancom's anemia too early to be evaluated.C. Five patients with various types of leukemia underwent HLA-mached alogeneic BMT and in all cases, hematologic and immunologic functions have been reconstituted.