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Absence of regulatory T-cell control of TH1 and TH17 cells is responsible for the autoimmune-mediated pathology in chronic graft-versus-host disease. Blood 2007 Nov 15;110(10):3804-13

Date

08/19/2007

Pubmed ID

17693581

Pubmed Central ID

PMC2077325

DOI

10.1182/blood-2007-05-091074

Scopus ID

2-s2.0-36348980530   167 Citations

Abstract

Graft-versus-host disease (GVHD) remains the major complication after allogeneic bone marrow transplantation (BMT). The process whereby acute GVHD mediated by alloreactive donor T cells transitions into chronic GVHD, which is characterized by prominent features of auto-immunity, has long been unresolved. In this study, we demonstrate that GVHD-associated autoimmunity and, by extension, chronic GVHD is attributable to the progressive loss of CD4(+)CD25(+)Foxp3(+) regulatory T cells during the course of acute GVHD. This leads to the expansion of donor-derived CD4(+) T cells with T(H)1 and T(H)17 cytokine phenotypes that release proinflammatory cytokines and cause autoimmune-mediated pathological damage. These T cells are present early after transplantation, indicating that the pathophysiological events that lead to chronic GVHD are set in motion during the acute phase of GVHD. We conclude that the absence of CD4(+)CD25(+) regulatory T cells coupled with unregulated T(H)1 and T(H)17 cells leads to the development of autoimmunity and that donor-derived T(H)1 and T(H)17 cells serve as the nexus between acute and chronic GVHD.

Author List

Chen X, Vodanovic-Jankovic S, Johnson B, Keller M, Komorowski R, 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
Bryon D. Johnson PhD Professor in the Medicine department at Medical College of Wisconsin




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

Animals
Autoimmunity
CD4-Positive T-Lymphocytes
Chronic Disease
Forkhead Transcription Factors
Graft vs Host Disease
Inflammation Mediators
Interleukin-2 Receptor alpha Subunit
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
T-Lymphocytes, Regulatory
Th1 Cells
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75