title: Development of tolerance after haplocompatible T-depleted bone marrow transplantation.
abstract: We evaluated proliferative responses in mixed lymphocyte cultures (MLC) following bone marrow transplantation (BMT) in 14 recipients of T cell-depleted haplo-compatible parental marrow: 11 for the treatment of severe combined immunodeficiency (SCID), 2 for leukemia and 1 for Wiskott-Aldrich syndrome (WAS). We compared the results obtained in 9 SCID patients and 1 WAS patient with split chimerism (T cells of donor origin, B cells and monocytes of recipient origin) to 4 patients (2 SCID and 2 leukemias) who were full chimeras (T, B and monocytes of donor origin). In the full chimeras, as with the fresh donor PBMC, fresh donor T cells did not proliferate in the MLC to recipient non-T cells (E-). In this group there were no differences (p > 0.2) between the responses of engrafted T and fresh donor T to recipient E- cells. We found tolerance of engrafted donor T cells to residual mismatched T cell-depleted (E-) recipient cells in the split chimera group. In this group the engrafted T cells had low or no responses in MLC to HLA mismatched E- host cells compared with fresh donor cells (p < 0.001). In 3 of 8 split chimera patients that we tested the addition of small numbers (5000-10,000) of freshly isolated donor T cells, irradiated or not, resulted in a two fold increase in the engrafted T cell response to recipient E- cells. In contrast, in 3 of 3 full chimeras tested, the addition of fresh donor T cells had no demonstrable effect on the response of engrafted T cells to recipient E-.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Postgraduate School of Haematology Farreras Valentí, Hospital Clinic, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Merino
authors.forename: Y
authors.initials: Y
authors.lastname: Dror
authors.forename: M
authors.initials: M
authors.lastname: Benkerrou
authors.forename: B W
authors.initials: BW
authors.lastname: Colombe
authors.forename: M J
authors.initials: MJ
authors.lastname: Cowan
mesh_terms: D000293:Adolescent; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002678:Chimera / Q000276:immunology; D005260:Female; D006238:Haploidy; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007938:Leukemia / Q000628:therapy; D008212:Lymphocyte Depletion; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D016511:Severe Combined Immunodeficiency / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014019:Tissue Donors; D014923:Wiskott-Aldrich Syndrome / Q000628:therapy