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Immunological lessons learnt from patients transplanted with fully mismatched stem cells
Immunological lessons learnt from patients transplanted with fully mismatched stem cells 1st Robert-A-Good-Society Symposium Touraine, J., Plotnicky, H., Roncarolo, M., Bacchetta, R., Gebuhrer, L. HUMANA PRESS INC. 2007: 201–9Abstract
Fully HLA-mismatched stem cells from human fetal livers were transplanted into 17 infants and two fetuses to treat severe combined immunodeficiency disease in 1976-2000. Donor cell engraftment and immunological reconstitution were obtained in 14/19 patients, three of whom have been extensively and repeatedly studied immunologically during prolonged follow-up. T-cells were derived totally from donor cells; B-cells and antigen-presenting cells (APC) remained mainly of host origin. Due to class I and II mismatches between T-cells and all other cells (APC, B-cells, virus-infected target cells), limitations in the defense against infections in vivo and in T-cell functions in vitro (helper and cytotoxic activities) were predicted; however, these did not occur. Anti-tetanus toxoid responses (including specific antibody production) developed despite HLA disparities between T-cells and B-cells or APC in the chimeric children. Similarly, cytotoxic T-cells (of donor HLA phenotype) recognized host Epstein-Barr virus-infected target cells. Recognition of antigenic peptide by T-cells under these conditions involved presentation by host allogeneic HLA molecules and not by self HLA antigens. Tolerance to donor antigens was acquired by clonal deletion; tolerance to host antigens existed despite the presence of many host-reactive T-cells and involved clonal anergy.
View details for DOI 10.1007/s12026-007-0002-6
View details for Web of Science ID 000250372300024
View details for PubMedID 17917026