© The Rockefeller University Press, 0022-1007/1999/4/1329/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 8, April 19, 1999 1329-1342
The Effect of Graft-versus-Host Disease on T Cell Production and Homeostasis
Gaël Dulude,
Denis-Claude Roy, and
Claude Perreault
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 Vβ 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.
Key Words: adoptive transfer bone marrow transplantation cell survival thymus gland T lymphocyte subsets
Address correspondence to Claude Perreault, Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital, 5415 de l'Assomption Blvd., Montreal, H1T 2M4 Quebec, Canada. Phone: 514-252-3557; Fax: 514-252-3430; E-mail: cperreau{at}hmr.qc.ca
Abbreviations used: BrdU, 5-bromo-2'-deoxyuridine.

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