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Enhancement of thymopoiesis after bone marrow transplant by in vivo
interleukin-7
E Bolotin, M Smogorzewska, S Smith, M Widmer and K Weinberg
Department of Pediatrics, Childrens Hospital Los Angeles, University of
Southern California School of Medicine, Los Angeles, USA.
Bone marrow transplantation (BMT) is followed by a period of profound
immune deficiency, during which new T lymphocytes are generated from either
stem cells or immature thymic progenitors. Interleukin-7 (IL-7) induces
proliferation and differentiation of immature thymocytes. We examined
whether the in vivo administration of IL-7 to mice receiving BMT would
alter thymic reconstitution. Lethally irradiated C57BL/6 mice received
syngeneic BMT, followed by either IL-7 or placebo from days 5 to 18
post-BMT. At day 28, BMT recipients that had not received IL-7 had profound
thymic hypoplasia (< 5% of normal), with relative increases in the
numbers of immature thymocytes, decreased numbers of mature peripheral
(splenic) T lymphocytes, and severely impaired T- and B-cell function. In
contrast, transplanted mice treated with IL-7 had normalization of thymic
cellularity, with normal proportions of thymic subsets and T-cell receptor
beta variable gene (TCRV beta) usage, normal numbers of peripheral CD4+ T
lymphocytes, and improved antigen- specific T- and B-cell function. In the
BMT-IL-7 mice, there was an eightfold increase in the number of immature
CD3-CD4-CD8- thymocytes in G2-M of the cell cycle, indicating that
restoration of thymic cellularity was due to enhanced proliferation of
immature thymic progenitors. Similar effects following IL-7 administration
were also observed when donor bone marrow was depleted of mature T
lymphocytes, indicating that IL-7 administration affected immature
hematopoietic progenitors. IL-7 promotes thymic reconstitution after BMT,
and may be useful in preventing post-BMT immune deficiency.
Volume 88,
Issue 5,
pp. 1887-1894,
09/01/1996
Copyright © 1996 by The American Society of Hematology
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