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J. Exp. Med.,
Volume 189, Number 8, April 19, 1999 1329-1342
By
From the Department of Medicine, University of Montreal, and Research Center,
Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada H1T 2M4
The aim of this work was to decipher how graft-versus-host disease (GVHD) affects T cell production and homeostasis. In GVHD+ mice, thymic output was decreased fourfold relative to
normal mice, but was sufficient to maintain a T cell repertoire with normal diversity in terms
of V
usage. Lymphoid hypoplasia in GVHD+ mice was caused mainly by a lessened expansion of the peripheral postthymic T cell compartment. In 5-bromo-2'-deoxyuridine pulse-chase experiments, resident T cells in the spleen of GVHD+ mice showed a normal turnover rate (proliferation and half-life). When transferred into thymectomized GVHD
secondary hosts, T
cells from GVHD+ mice expanded normally. In contrast, normal T cells failed to expand when
injected into GVHD+ mice. Thus, the reduced size of the postthymic compartment in GVHD+
mice was not due to an intrinsic lymphocyte defect, but to an extrinsic microenvironment abnormality. We suggest that this extrinsic anomaly is consistent with a reduced number of functional peripheral T cell niches. Therefore, our results show that GVHD-associated T cell hypoplasia is largely caused by a perturbed homeostasis of the peripheral compartment. Furthermore,
they suggest that damage to the microenvironment of secondary lymphoid organs may represent
an heretofore unrecognized cause of acquired T cell hypoplasia.
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