Maintenance of CD8+ T-cell anergy by CD4+CD25+ regulatory T cells in chronic graft-versus-host disease.
In a murine model of systemic lupus erythematosus (SLE)-like chronic graft-versus-host disease (cGVHD), donor CD8+ T cells rapidly fall into anergy to host cells, while donor CD4+ T cells hyperactivate B cells and break B-cell tolerance to self-Ags in the recipient mouse. The functional recovery of donor CD8+ T cells can result in the conversion of cGVHD to acute GVHD (aGVHD), indicating that donor CD8+ T-cell anergy is a restriction factor in the development of cGVHD. In this report, we present evidence that donor CD4+CD25+ regulatory T cells (Treg cells) are critical in maintaining the donor CD8+ T-cell anergy and thus suppressing the development of aGVHD in mice that are naturally prone to cGVHD. Our results provide a novel insight into the role of Treg cells in determining cGVHD versus aGVHD.
Kim
Juyang
J
The Immunomodulation Research Center, University of Ulsan, Ulsan 680-749, Korea.
Kim
Hye J
HJ
Choi
Woon S
WS
Nam
Seok H
SH
Cho
Hong R
HR
Kwon
Byungsuk
B
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D017635:Clonal Anergy / Q000502:physiology*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D007108:Immune Tolerance / Q000502:physiology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D053645:Interleukin-2 Receptor alpha Subunit