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Blood, 15 February 2002, Vol. 99, No. 4, pp. 1442-1448
TRANSPLANTATION
Rapid establishment of dendritic cell chimerism in allogeneic
hematopoietic cell transplant recipients
Susanne Auffermann-Gretzinger,
Izidore S. Lossos,
Tamara A. Vayntrub,
Wendy Leong,
F. Carl Grumet,
Karl G. Blume,
Keith E. Stockerl-Goldstein,
Ronald Levy, and
Judith A. Shizuru
From the Division of Oncology and Bone Marrow
Transplantation, Department of Medicine, and the Blood Center, Stanford
University Medical Center, CA.
Regeneration of hematopoiesis after allogeneic hematopoietic cell
transplantation (HCT) involves conversion of the recipient's immune
system to donor type. It is likely that distinct cell lineages in the
recipient reconstitute at different rates. Dendritic cells (DCs) are a
subset of hematopoietic cells that function as a critical component of
antigen-specific immune responses because they modulate T-cell
activation, as well as induction of tolerance. Mature DCs are
transferred with hematopoietic grafts and subsequently arise de novo.
Little information exists about engraftment kinetics and turnover of
this cell population in patients after allogeneic HCT. This study
examined the kinetics of DC chimerism in patients who underwent matched
sibling allogeneic HCT. T-cell, B-cell, and myelocytic and monocytic
chimerism were also studied. Peripheral blood cells were analyzed at
defined intervals after transplantation from 19 patients with various
hematologic malignancies after treatment with myeloablative or
nonmyeloablative preparatory regimens. Cell subsets were isolated
before analysis of chimerism. Despite the heterogeneity of the patient
population and preparatory regimens, all showed rapid and consistent
development of DC chimerism. By day +14 after transplantation
approximately 80% of DCs were of donor origin with steady increase to
more than 95% by day +56. Earlier time points were examined in a
subgroup of patients who had undergone nonmyeloablative
conditioning and transplantation. These data suggest that a major
proportion of blood DCs early after transplantation is donor-derived
and that donor chimerism develops rapidly. This information has
potential implications for manipulation of immune responses after
allogeneic HCT.
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