TY - JOUR
T1 - Immunologic Resolution of Human Chronic Graft-versus-Host Disease
AU - Mahadeo, Kris M.
AU - Masinsin, Bernadette
AU - Kapoor, Neena
AU - Shah, Ami J.
AU - Abdel-Azim, Hisham
AU - Parkman, Robertson
N1 - Publisher Copyright:
© 2014 American Society for Blood and Marrow Transplantation.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - To determine the role of regulatory T lymphocytes (Tregs) in the pathogenesis of human chronic graft-versus-host disease (GVHD) and its clinical resolution, we evaluated long-term recipients of pediatric allogeneic hematopoietic stem cell transplantation (HSCT). Seventy-one recipients were evaluated, 30 of whom had a history of chronic GVHD, including 16 with active chronic GVHD and 14 with resolved chronic GVHD. There were no significant clinical differences and no differences in the frequency of Tregs (CD4+, CD127-, CD25+) between the recipients with active chronic GVHD and those with resolved chronic GVHD. Using the Miyara/Sakaguchi classification scheme to identify functional Tregs, a decreased frequency of functional resting Tregs (rTregs) was identified in recipients with active chronic GVHD (P=009 compared with normal donors; P=001 compared with HSCT recipients without history of chronic GVHD; P=005 compared with recipients with resolved chronic GVHD). The frequency and number of recent thymic emigrants in rTregs were normal in recipients with resolved chronic GVHD, but persistently decreased in recipients with active chronic GVHD. These results support the hypothesis that the reestablishment of normal numbers of functional rTregs is required for the clinical resolution of chronic GVHD.
AB - To determine the role of regulatory T lymphocytes (Tregs) in the pathogenesis of human chronic graft-versus-host disease (GVHD) and its clinical resolution, we evaluated long-term recipients of pediatric allogeneic hematopoietic stem cell transplantation (HSCT). Seventy-one recipients were evaluated, 30 of whom had a history of chronic GVHD, including 16 with active chronic GVHD and 14 with resolved chronic GVHD. There were no significant clinical differences and no differences in the frequency of Tregs (CD4+, CD127-, CD25+) between the recipients with active chronic GVHD and those with resolved chronic GVHD. Using the Miyara/Sakaguchi classification scheme to identify functional Tregs, a decreased frequency of functional resting Tregs (rTregs) was identified in recipients with active chronic GVHD (P=009 compared with normal donors; P=001 compared with HSCT recipients without history of chronic GVHD; P=005 compared with recipients with resolved chronic GVHD). The frequency and number of recent thymic emigrants in rTregs were normal in recipients with resolved chronic GVHD, but persistently decreased in recipients with active chronic GVHD. These results support the hypothesis that the reestablishment of normal numbers of functional rTregs is required for the clinical resolution of chronic GVHD.
KW - Chronic graft-versus-host disease
KW - Regulatory T lymphocytes
KW - Thymic function
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U2 - 10.1016/j.bbmt.2014.06.030
DO - 10.1016/j.bbmt.2014.06.030
M3 - Article
C2 - 24979733
AN - SCOPUS:84912530699
SN - 1083-8791
VL - 20
SP - 1508
EP - 1515
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 10
ER -