Increased mitochondrial apoptotic priming of human regulatory T cells after allogeneic hematopoietic stem cell transplantation

Kazuyuki Murase, Haesook T. Kim, O. R. Gregory Bascug, Yutaka Kawano, Jeremy Ryan, Ken-ichi Matsuoka, Matthew S. Davids, John Koreth, Vincent T. Ho, Corey Cutler, Philippe Armand, Edwin P. Alyea, Bruce R. Blazar, Joseph H. Antin, Robert J. Soiffer, Anthony Letai, Jerome Ritz

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

CD4 regulatory T cells play a critical role in establishment of immune tolerance and prevention of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. The recovery and maintenance of regulatory T cells is dependent on homeostatic factors including the generation of naïve regulatory T cells from hematopoietic precursor cells, the proliferation and expansion of mature regulatory T cells, and the survival of regulatory T cells in vivo. In this study, quantitation of mitochondrial apoptotic priming was used to compare susceptibility of regulatory T cells, conventional CD4 T cells and CD8 T cells to intrinsic pathway apoptosis in 57 patients after allo-geneic hematopoietic stem cell transplantation and 25 healthy donors. In healthy donors, regulatory T cells are more susceptible to mitochondrial priming than conventional T cells. Mitochondrial priming is increased after hematopoietic stem cell transplantation in all T-cell subsets and particularly in patients with chronic graft-versus-host disease. Regulatory T cells express high levels of CD95 and are also more susceptible than conventional T cells to apoptosis through the extrinsic pathway. However, CD95 expression and extrinsic pathway apoptosis is not increased after hematopoietic stem cell transplantation. Decreased expression of BCL2 and increased expression of BIM, a mitochondrial cell death activator protein, in regulatory T cells contributes to increased mitochon-drial priming in this T-cell subset but additional factors likely contribute to increased mitochondrial priming following hematopoietic stem cell transplantation.

Original languageEnglish
Pages (from-to)1499-1508
Number of pages10
JournalHaematologica
Volume99
Issue number9
DOIs
Publication statusPublished - Sep 1 2014

Fingerprint

Hematopoietic Stem Cell Transplantation
Regulatory T-Lymphocytes
T-Lymphocytes
T-Lymphocyte Subsets
Graft vs Host Disease
Apoptosis
Tissue Donors
T-Lymphoid Precursor Cells
Immune Tolerance
Cell Survival
Cell Death
Maintenance
Cell Proliferation

ASJC Scopus subject areas

  • Hematology

Cite this

Increased mitochondrial apoptotic priming of human regulatory T cells after allogeneic hematopoietic stem cell transplantation. / Murase, Kazuyuki; Kim, Haesook T.; Gregory Bascug, O. R.; Kawano, Yutaka; Ryan, Jeremy; Matsuoka, Ken-ichi; Davids, Matthew S.; Koreth, John; Ho, Vincent T.; Cutler, Corey; Armand, Philippe; Alyea, Edwin P.; Blazar, Bruce R.; Antin, Joseph H.; Soiffer, Robert J.; Letai, Anthony; Ritz, Jerome.

In: Haematologica, Vol. 99, No. 9, 01.09.2014, p. 1499-1508.

Research output: Contribution to journalArticle

Murase, K, Kim, HT, Gregory Bascug, OR, Kawano, Y, Ryan, J, Matsuoka, K, Davids, MS, Koreth, J, Ho, VT, Cutler, C, Armand, P, Alyea, EP, Blazar, BR, Antin, JH, Soiffer, RJ, Letai, A & Ritz, J 2014, 'Increased mitochondrial apoptotic priming of human regulatory T cells after allogeneic hematopoietic stem cell transplantation', Haematologica, vol. 99, no. 9, pp. 1499-1508. https://doi.org/10.3324/haematol.2014.104166
Murase, Kazuyuki ; Kim, Haesook T. ; Gregory Bascug, O. R. ; Kawano, Yutaka ; Ryan, Jeremy ; Matsuoka, Ken-ichi ; Davids, Matthew S. ; Koreth, John ; Ho, Vincent T. ; Cutler, Corey ; Armand, Philippe ; Alyea, Edwin P. ; Blazar, Bruce R. ; Antin, Joseph H. ; Soiffer, Robert J. ; Letai, Anthony ; Ritz, Jerome. / Increased mitochondrial apoptotic priming of human regulatory T cells after allogeneic hematopoietic stem cell transplantation. In: Haematologica. 2014 ; Vol. 99, No. 9. pp. 1499-1508.
@article{fca68ce3f8584248a6b01b9c467f47cf,
title = "Increased mitochondrial apoptotic priming of human regulatory T cells after allogeneic hematopoietic stem cell transplantation",
abstract = "CD4 regulatory T cells play a critical role in establishment of immune tolerance and prevention of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. The recovery and maintenance of regulatory T cells is dependent on homeostatic factors including the generation of na{\"i}ve regulatory T cells from hematopoietic precursor cells, the proliferation and expansion of mature regulatory T cells, and the survival of regulatory T cells in vivo. In this study, quantitation of mitochondrial apoptotic priming was used to compare susceptibility of regulatory T cells, conventional CD4 T cells and CD8 T cells to intrinsic pathway apoptosis in 57 patients after allo-geneic hematopoietic stem cell transplantation and 25 healthy donors. In healthy donors, regulatory T cells are more susceptible to mitochondrial priming than conventional T cells. Mitochondrial priming is increased after hematopoietic stem cell transplantation in all T-cell subsets and particularly in patients with chronic graft-versus-host disease. Regulatory T cells express high levels of CD95 and are also more susceptible than conventional T cells to apoptosis through the extrinsic pathway. However, CD95 expression and extrinsic pathway apoptosis is not increased after hematopoietic stem cell transplantation. Decreased expression of BCL2 and increased expression of BIM, a mitochondrial cell death activator protein, in regulatory T cells contributes to increased mitochon-drial priming in this T-cell subset but additional factors likely contribute to increased mitochondrial priming following hematopoietic stem cell transplantation.",
author = "Kazuyuki Murase and Kim, {Haesook T.} and {Gregory Bascug}, {O. R.} and Yutaka Kawano and Jeremy Ryan and Ken-ichi Matsuoka and Davids, {Matthew S.} and John Koreth and Ho, {Vincent T.} and Corey Cutler and Philippe Armand and Alyea, {Edwin P.} and Blazar, {Bruce R.} and Antin, {Joseph H.} and Soiffer, {Robert J.} and Anthony Letai and Jerome Ritz",
year = "2014",
month = "9",
day = "1",
doi = "10.3324/haematol.2014.104166",
language = "English",
volume = "99",
pages = "1499--1508",
journal = "Haematologica",
issn = "0390-6078",
publisher = "Ferrata Storti Foundation",
number = "9",

}

TY - JOUR

T1 - Increased mitochondrial apoptotic priming of human regulatory T cells after allogeneic hematopoietic stem cell transplantation

AU - Murase, Kazuyuki

AU - Kim, Haesook T.

AU - Gregory Bascug, O. R.

AU - Kawano, Yutaka

AU - Ryan, Jeremy

AU - Matsuoka, Ken-ichi

AU - Davids, Matthew S.

AU - Koreth, John

AU - Ho, Vincent T.

AU - Cutler, Corey

AU - Armand, Philippe

AU - Alyea, Edwin P.

AU - Blazar, Bruce R.

AU - Antin, Joseph H.

AU - Soiffer, Robert J.

AU - Letai, Anthony

AU - Ritz, Jerome

PY - 2014/9/1

Y1 - 2014/9/1

N2 - CD4 regulatory T cells play a critical role in establishment of immune tolerance and prevention of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. The recovery and maintenance of regulatory T cells is dependent on homeostatic factors including the generation of naïve regulatory T cells from hematopoietic precursor cells, the proliferation and expansion of mature regulatory T cells, and the survival of regulatory T cells in vivo. In this study, quantitation of mitochondrial apoptotic priming was used to compare susceptibility of regulatory T cells, conventional CD4 T cells and CD8 T cells to intrinsic pathway apoptosis in 57 patients after allo-geneic hematopoietic stem cell transplantation and 25 healthy donors. In healthy donors, regulatory T cells are more susceptible to mitochondrial priming than conventional T cells. Mitochondrial priming is increased after hematopoietic stem cell transplantation in all T-cell subsets and particularly in patients with chronic graft-versus-host disease. Regulatory T cells express high levels of CD95 and are also more susceptible than conventional T cells to apoptosis through the extrinsic pathway. However, CD95 expression and extrinsic pathway apoptosis is not increased after hematopoietic stem cell transplantation. Decreased expression of BCL2 and increased expression of BIM, a mitochondrial cell death activator protein, in regulatory T cells contributes to increased mitochon-drial priming in this T-cell subset but additional factors likely contribute to increased mitochondrial priming following hematopoietic stem cell transplantation.

AB - CD4 regulatory T cells play a critical role in establishment of immune tolerance and prevention of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. The recovery and maintenance of regulatory T cells is dependent on homeostatic factors including the generation of naïve regulatory T cells from hematopoietic precursor cells, the proliferation and expansion of mature regulatory T cells, and the survival of regulatory T cells in vivo. In this study, quantitation of mitochondrial apoptotic priming was used to compare susceptibility of regulatory T cells, conventional CD4 T cells and CD8 T cells to intrinsic pathway apoptosis in 57 patients after allo-geneic hematopoietic stem cell transplantation and 25 healthy donors. In healthy donors, regulatory T cells are more susceptible to mitochondrial priming than conventional T cells. Mitochondrial priming is increased after hematopoietic stem cell transplantation in all T-cell subsets and particularly in patients with chronic graft-versus-host disease. Regulatory T cells express high levels of CD95 and are also more susceptible than conventional T cells to apoptosis through the extrinsic pathway. However, CD95 expression and extrinsic pathway apoptosis is not increased after hematopoietic stem cell transplantation. Decreased expression of BCL2 and increased expression of BIM, a mitochondrial cell death activator protein, in regulatory T cells contributes to increased mitochon-drial priming in this T-cell subset but additional factors likely contribute to increased mitochondrial priming following hematopoietic stem cell transplantation.

UR - http://www.scopus.com/inward/record.url?scp=84907356372&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907356372&partnerID=8YFLogxK

U2 - 10.3324/haematol.2014.104166

DO - 10.3324/haematol.2014.104166

M3 - Article

C2 - 24859877

AN - SCOPUS:84907356372

VL - 99

SP - 1499

EP - 1508

JO - Haematologica

JF - Haematologica

SN - 0390-6078

IS - 9

ER -