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Blood, Vol. 94 No. 12 (December 15), 1999:
pp. 4358-4369
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
Barbara C. Godthelp,
Maarten J.D. van Tol,
Jaak M. Vossen, and
Peter J. van den Elsen
From the Departments of Pediatrics and Immunohematology and Blood
Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
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 repertoires in pediatric allo-BMT recipients
treated for leukemia. We observed a lack 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 year
after allo-BMT, normalization was observed of TCR CDR3 size complexity
in almost all recipients. Analysis of the antigen-specific T-cell
repertoire at 1 year after BMT showed that the T cells responding to
tetanus toxoid (TT) differed in TCR gene segment usage and in amino
acid composition of the CDR3 region when comparing the recipient with
the donor. Moreover, the TT-specific TCR repertoire was found to be
stable within a given allo-BMT recipient, because TT-specific T cells
with completely identical TCRs were found at 3 consecutive years after
transplantation. These observations suggest an important role for
T-cell selection processes in the complete restoration of the T-cell
immune repertoire in children after allo-BMT.
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