T-cell immune reconstitution in pediatric leukemia patients after allogeneic bone marrow transplantation with T-cell-depleted or unmanipulated grafts: Evaluation of overall and antigen-specific T-cell repertoires

To evaluate the role of T-cell selection in the thymus and/or periphery in T-cell immune reconstitution after allogeneic bone marrow transplantation ( allo-BMT), we have analyzed the overall and antigen-specific T-cell reperto ires in pediatric allo-BMT recipients treated for leukemia. We observed a l ack of overall T-cell receptor (TCR) diversity in the repopulating T cells at 3 months after allo-BMT, as was deduced from complementarity determining region 3 (CDR3) size distribution patterns displaying reduced complexity. This was noted particularly in recipients of a T-cell-depleted (TCD) graft and, to a lesser extent, also in recipients of unmanipulated grafts. At 1 y ear after allo-BMT, normalization was observed of TCR CDR3 size complexity in almost all recipients. Analysis of the antigen-specific T-cell repertoir e at 1 year after BMT showed that the T cells responding to tetanus toroid (TT) differed in TCR gene segment usage and in amino acid composition of th e CDR3 region when comparing the recipient with the donor. Moreover, the TT -specific TCR repertoire was found to he stable within a given allo-BMT rec ipient, because TT-specific T cells with completely identical TCRs were fou nd at 3 consecutive years after transplantation. These observations suggest an important role for T-cell selection processes in the complete restorati on of the T-cell immune repertoire in children after allo-BMT. (C) 1999 by The American Society of Hematology.