Abstract
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.
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Touraine, JL., Plotnicky, H., Roncarolo, MG. et al. Immunological lessons learnt from patients transplanted with fully mismatched stem cells. Immunol Res 38, 201–209 (2007). https://doi.org/10.1007/s12026-007-0002-6
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DOI: https://doi.org/10.1007/s12026-007-0002-6