Development of tolerance after haplocompatible T-depleted bone marrow transplantation

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)