Low telomerase activity in CD4 + regulatory T cells in patients with severe chronic GVHD after hematopoietic stem cell transplantation

Yutaka Kawano, Haesook T. Kim, Ken-ichi Matsuoka, Gregory Bascug, Sean McDonough, Vincent T. Ho, Corey Cutler, John Koreth, Edwin P. Alyea, Joseph H. Antin, Robert J. Soiffer, Jerome Ritz

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

CD4 +CD25 +Foxp3 + regulatory T cells (Treg) play an important role in the control of chronic graft-versus-host disease (cGVHD). In this study, we examined telomere length and telomerase activity of Treg and conventional CD4 + T cells (Tcon) in 61 patients who survived more than 2 years after allogeneic hematopoietic stem cell transplantation. Cell proliferation and expression of Bcl-2 were also measured in each subset. Treg telomere length was shorter and Treg telomerase activity was increased compared with Tcon (P <.0001). After transplantation, Treg were also more highly proliferative than Tcon (P <.0001). Treg number, telomerase activity, and expression of Bcl-2 were each inversely associated with severity of cGVHD. These data indicate that activation of telomerase is not sufficient to prevent telomere shortening in highly proliferative Treg. However, telomerase activation is associated with increased Bcl-2 expression and higher Treg numbers in patients with no or mild cGVHD. In contrast, patients with moderate or severe cGVHD have fewer Treg with lower levels of telomerase activity and Bcl-2 expression. These results suggest that failure to activate Treg telomerase may restrict proliferative capacity and increase apoptotic susceptibility, resulting in the loss of peripheral tolerance and the development of cGVHD.

Original languageEnglish
Pages (from-to)5021-5030
Number of pages10
JournalBlood
Volume118
Issue number18
DOIs
Publication statusPublished - Nov 3 2011
Externally publishedYes

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T-cells
Telomerase
Hematopoietic Stem Cell Transplantation
Regulatory T-Lymphocytes
Stem cells
Graft vs Host Disease
Grafts
Telomere
Chemical activation
Peripheral Tolerance
Telomere Shortening
Cell proliferation
Transplantation
Cell Proliferation
T-Lymphocytes

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Low telomerase activity in CD4 + regulatory T cells in patients with severe chronic GVHD after hematopoietic stem cell transplantation. / Kawano, Yutaka; Kim, Haesook T.; Matsuoka, Ken-ichi; Bascug, Gregory; McDonough, Sean; Ho, Vincent T.; Cutler, Corey; Koreth, John; Alyea, Edwin P.; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome.

In: Blood, Vol. 118, No. 18, 03.11.2011, p. 5021-5030.

Research output: Contribution to journalArticle

Kawano, Y, Kim, HT, Matsuoka, K, Bascug, G, McDonough, S, Ho, VT, Cutler, C, Koreth, J, Alyea, EP, Antin, JH, Soiffer, RJ & Ritz, J 2011, 'Low telomerase activity in CD4 + regulatory T cells in patients with severe chronic GVHD after hematopoietic stem cell transplantation', Blood, vol. 118, no. 18, pp. 5021-5030. https://doi.org/10.1182/blood-2011-06-362137
Kawano, Yutaka ; Kim, Haesook T. ; Matsuoka, Ken-ichi ; Bascug, Gregory ; McDonough, Sean ; Ho, Vincent T. ; Cutler, Corey ; Koreth, John ; Alyea, Edwin P. ; Antin, Joseph H. ; Soiffer, Robert J. ; Ritz, Jerome. / Low telomerase activity in CD4 + regulatory T cells in patients with severe chronic GVHD after hematopoietic stem cell transplantation. In: Blood. 2011 ; Vol. 118, No. 18. pp. 5021-5030.
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