The effect of graft-versus-host disease on T cell production and homeostasis.
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 Vbeta 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.
Dulude
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Department of Medicine, University of Montreal, and Research Center, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada H1T 2M4.
Roy
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DC
Perreault
C
C
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D001973:Bromodeoxyuridine / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002455:Cell Division; D002678:Chimera; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology
D011948:Receptors, Antigen, T-Cell; D001973:Bromodeoxyuridine