Immunologic Resolution of Human Chronic Graft-versus-Host Disease

Kris M. Mahadeo, Bernadette Masinsin, Neena Kapoor, Ami J. Shah, Hisham Abdel-Azim, Robertson Parkman

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1508-1515
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume20
Issue number10
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

Fingerprint

Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Regulatory T-Lymphocytes
Tissue Donors
Pediatrics

Keywords

  • Chronic graft-versus-host disease
  • Regulatory T lymphocytes
  • Thymic function

ASJC Scopus subject areas

  • Transplantation
  • Hematology
  • Medicine(all)

Cite this

Mahadeo, K. M., Masinsin, B., Kapoor, N., Shah, A. J., Abdel-Azim, H., & Parkman, R. (2014). Immunologic Resolution of Human Chronic Graft-versus-Host Disease. Biology of Blood and Marrow Transplantation, 20(10), 1508-1515. https://doi.org/10.1016/j.bbmt.2014.06.030

Immunologic Resolution of Human Chronic Graft-versus-Host Disease. / Mahadeo, Kris M.; Masinsin, Bernadette; Kapoor, Neena; Shah, Ami J.; Abdel-Azim, Hisham; Parkman, Robertson.

In: Biology of Blood and Marrow Transplantation, Vol. 20, No. 10, 01.10.2014, p. 1508-1515.

Research output: Contribution to journalArticle

Mahadeo, KM, Masinsin, B, Kapoor, N, Shah, AJ, Abdel-Azim, H & Parkman, R 2014, 'Immunologic Resolution of Human Chronic Graft-versus-Host Disease', Biology of Blood and Marrow Transplantation, vol. 20, no. 10, pp. 1508-1515. https://doi.org/10.1016/j.bbmt.2014.06.030
Mahadeo KM, Masinsin B, Kapoor N, Shah AJ, Abdel-Azim H, Parkman R. Immunologic Resolution of Human Chronic Graft-versus-Host Disease. Biology of Blood and Marrow Transplantation. 2014 Oct 1;20(10):1508-1515. https://doi.org/10.1016/j.bbmt.2014.06.030
Mahadeo, Kris M. ; Masinsin, Bernadette ; Kapoor, Neena ; Shah, Ami J. ; Abdel-Azim, Hisham ; Parkman, Robertson. / Immunologic Resolution of Human Chronic Graft-versus-Host Disease. In: Biology of Blood and Marrow Transplantation. 2014 ; Vol. 20, No. 10. pp. 1508-1515.
@article{e257760891454d72a5d30d18e9d7b9b8,
title = "Immunologic Resolution of Human Chronic Graft-versus-Host Disease",
abstract = "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.",
keywords = "Chronic graft-versus-host disease, Regulatory T lymphocytes, Thymic function",
author = "Mahadeo, {Kris M.} and Bernadette Masinsin and Neena Kapoor and Shah, {Ami J.} and Hisham Abdel-Azim and Robertson Parkman",
year = "2014",
month = "10",
day = "1",
doi = "10.1016/j.bbmt.2014.06.030",
language = "English (US)",
volume = "20",
pages = "1508--1515",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "10",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=84912530699&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84912530699&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2014.06.030

DO - 10.1016/j.bbmt.2014.06.030

M3 - Article

VL - 20

SP - 1508

EP - 1515

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 10

ER -