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Homeostatic expansion and repertoire regeneration of donor T cells during graft versus host disease is constrained by the host environment. Blood 2007 Jun 15;109(12):5502-10 PMID: 17347406 PMCID: PMC1890817

Pubmed ID

17347406

Abstract

Graft versus host disease (GVHD) typically results in impaired T-cell reconstitution characterized by lymphopenia and repertoire skewing. One of the major causes of inadequate T-cell reconstitution is that T-cell survival and expansion in the periphery are impaired. In this report, we have performed adoptive transfer studies to determine whether the quantitative reduction in T-cell numbers is due to an intrinsic T-cell defect or whether the environmental milieu deleteriously affects T-cell expansion. These studies demonstrate that T cells obtained from animals with graft-versus-host disease (GVHD) are capable of significant expansion and renormalization of an inverted CD4/CD8 ratio when they are removed from this environment. Moreover, these cells can generate complex T-cell repertoires early after transplantation and are functionally competent to respond to third-party alloantigens. Our data indicate that T cells from mice undergoing GVHD can respond to homeostatic signals in the periphery and are not intrinsically compromised once they are removed from the GVHD environment. We thereby conclude that the host environment and not an intrinsic T-cell defect is primarily responsible for the lack of effective T-cell expansion and diversification of complex T-cell repertoires that occurs during GVHD.

Author List

Gorski J, Chen X, Gendelman M, Yassai M, Krueger A, Tivol E, Logan B, Komorowski R, Vodanovic-Jankovic S, Drobyski WR

Authors

Xiao Chen MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin
William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Brent R. Logan PhD Director, Professor in the Institute for Health and Equity department at Medical College of Wisconsin




Scopus

2-s2.0-34249979259   13 Citations

MESH terms used to index this publication - Major topics in bold

Adoptive Transfer
Animals
Cell Proliferation
Graft vs Host Disease
Hemostasis
Lymphocyte Culture Test, Mixed
Mice
Regeneration
T-Cell Antigen Receptor Specificity
T-Lymphocytes
jenkins-FCD Prod-296 4db9d02597e0a2e889e230f853b641c12f1c3ee3