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Blood, 15 December 2000, Vol. 96, No. 13, pp. 4344-4349
TRANSPLANTATION
Similar pattern of thymic-dependent T-cell reconstitution in
infants with severe combined immunodeficiency after human leukocyte
antigen (HLA)-identical and HLA-nonidentical stem cell
transplantation
Susanna M. Müller,
Thomas Kohn,
Ansgar S. Schulz,
Klaus-Michael Debatin, and
Wilhelm Friedrich
From the Department of Pediatrics, University Hospital
of Ulm, Ulm, Germany.
Donor T cells after stem cell transplantation reconstitute by 2 different pathways: by expansion from grafted, mature T cells and by
intrathymic maturation from progenitor cells. This study characterized
thymic-dependent reconstitution of CD4+ T cells following
different transplant modalities in patients with severe combined
immunodeficiency (SCID). Three groups of patients were studied: one
group after transplantation from human leukocyte antigen
(HLA)-identical siblings with unmanipulated grafts without
conditioning, a second group after transplantation from
HLA-nonidentical parents with T-cell-depleted grafts without preconditioning, and a third group with prior conditioning.
Reconstitution of the T-cell compartment was monitored by determining
the expression of CD45 isoforms by developing CD4+ cells in
the peripheral blood and in discriminating expanded (CD45RO+) and newly generated (CD45RA+) T
cells. Concomitantly, changes in the size of the thymus were evaluated
sequentially by ultrasonography. Reconstitution of
CD4+CD45RA+ cells was delayed in all patients
for several months, including patients after HLA-identical
transplantation, and was always paralleled by normalization of
the size of the thymus. No engraftment of donor progenitor cells was
observed, as studied in one patient transplanted without
conditioning. CD4+CD45RO+ cells were
detected early after transplantation only in patients given
unmanipulated grafts. The study showed that thymic-dependent T-cell
maturation in these patients with SCID runs an autonomous course,
independent of graft manipulation, of major HLA disparities, and of
whether conditioning is used or not. In addition, thymic maturation may
not require engraftment of donor-derived CD34+ cells in the marrow.
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