CD8+ Foxp3+ regulatory T cells are induced during graft-versus-host disease and mitigate disease severity. J Immunol 2012 Jul 01;189(1):464-74
Date
06/01/2012Pubmed ID
22649199Pubmed Central ID
PMC3381996DOI
10.4049/jimmunol.1200886Scopus ID
2-s2.0-84862901878 (requires institutional sign-in at Scopus site) 100 CitationsAbstract
Regulatory T cells (Tregs), in particular CD4(+) Foxp3(+) T cells, have been shown to play an important role in the maintenance of tolerance after allogeneic stem cell transplantation. In the current study, we have identified a population of CD8(+) Foxp3(+) T cells that are induced early during graft-versus-host disease (GVHD), constitute a significant percentage of the entire Treg population, and are present in all major GVHD target organs. These cells expressed many of the same cell surface molecules as found on CD4(+) Tregs and potently suppressed in vitro alloreactive T cell responses. Induction of these cells correlated positively with the degree of MHC disparity between donor and recipient and was significantly greater than that observed for CD4(+)-induced Tregs (iTregs) in nearly all tissue sites. Mice that lacked the ability to make both CD8(+) and CD4(+) iTregs had accelerated GVHD mortality compared with animals that were competent to make both iTreg populations. The absence of both iTreg populations was associated with significantly greater expansion of activated donor T cells and increased numbers of CD4(+) and CD8(+) T cells that secreted IFN-γ and IL-17. The presence of CD8(+) iTregs, however, was sufficient to prevent increased GVHD mortality in the complete absence of CD4(+) Tregs, indicating at least one functional iTreg population was sufficient to prevent an exacerbation in GVHD severity, and that CD8(+) iTregs could compensate for CD4(+) iTregs. These studies define a novel population of CD8(+) Tregs that play a role in mitigating the severity of GVHD after allogeneic stem cell transplantation.
Author List
Beres AJ, Haribhai D, Chadwick AC, Gonyo PJ, Williams CB, Drobyski WRAuthors
William R. Drobyski MD Professor in the Medicine department at Medical College of WisconsinCalvin B. Williams MD, PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBone Marrow Transplantation
CD8 Antigens
Cell Differentiation
Forkhead Transcription Factors
Graft vs Host Disease
Immune Tolerance
Lymphocyte Culture Test, Mixed
Mice
Mice, 129 Strain
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Mutant Strains
Mice, Transgenic
Severity of Illness Index
T-Lymphocyte Subsets
T-Lymphocytes, Regulatory
