International Journal of Hematology

, Volume 95, Issue 1, pp 86–94 | Cite as

Impaired regulatory T cell reconstitution in patients with acute graft-versus-host disease and cytomegalovirus infection after allogeneic bone marrow transplantation

  • Alain M. Ngoma
  • Kazuhiko Ikeda
  • Yuko Hashimoto
  • Kazuhiro Mochizuki
  • Hiroshi Takahashi
  • Hideki Sano
  • Hayato Matsumoto
  • Hideyoshi Noji
  • Syunnichi Saito
  • Atsushi Kikuta
  • Kazuei Ogawa
  • Mikio Ohtsuka
  • Masafumi Abe
  • Kenneth E. Nollet
  • Hitoshi Ohto
Original Article
First Online:
Received:
Revised:
Accepted:

Abstract

To elucidate the correlation between regulatory T cells (Tregs) and acute graft-versus-host disease (aGVHD) or cytomegalovirus infection following allogeneic bone marrow transplantation (allo-BMT), we evaluated either CD4+CD25high or FOXP3+ Treg-enriched cells in peripheral blood (PB) from 20 patients who received allo-BMT, and in biopsies of skin with aGVHD. Proportions of CD4+CD25highFOXP3+ cells in total lymphocytes, but not other types of T cells, were lower in patients who eventually developed grades II–IV aGVHD (n = 13) than in others (n = 7, P < 0.001). Proportions of CD62L+ cells in CD4+CD25high cells at day +30 were lower (P < 0.01) in patients who eventually showed cytomegalovirus viremia (n = 6) than in others (n = 14). Incidence of aGVHD (P < 0.05) or cytomegalovirus viremia (P < 0.05) was higher in patients without these complications, but with lower proportions of PB CD4+CD25highFOXP3+ cells at day +30 (n = 8) than in others (n = 8). However, in skin with aGVHD (n = 5), there was marked or slightly increased infiltration of CD8+ cells (P < 0.001) or CD3+FOXP3+ cells (P < 0.05), respectively, when compared with control (n = 5), resulting in threefold higher ratio of CD8+/CD3+FOXP3+ cells in aGVHD relative to controls (P < 0.05). Thus, impaired reconstitution of Tregs may be associated with aGVHD and CMV infection. Moreover, imbalance of Tregs and CD8+ cells may play a role in aGVHD tissue.

Keywords

Allogeneic bone marrow transplantation Regulatory T cells Tissue Acute GVHD Cytomegalovirus 
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Notes

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© The Japanese Society of Hematology 2011

Authors and Affiliations

  • Alain M. Ngoma
    • 1
  • Kazuhiko Ikeda
    • 1
    • 2
  • Yuko Hashimoto
    • 3
  • Kazuhiro Mochizuki
    • 4
  • Hiroshi Takahashi
    • 1
    • 2
  • Hideki Sano
    • 4
  • Hayato Matsumoto
    • 2
  • Hideyoshi Noji
    • 2
  • Syunnichi Saito
    • 1
  • Atsushi Kikuta
    • 4
  • Kazuei Ogawa
    • 2
  • Mikio Ohtsuka
    • 5
  • Masafumi Abe
    • 3
  • Kenneth E. Nollet
    • 1
  • Hitoshi Ohto
    • 1
  1. 1.Department of Transfusion Medicine and Transplantation ImmunologyFukushima Medical University School of MedicineFukushimaJapan
  2. 2.Department of Cardiology and HematologyFukushima Medical University School of MedicineFukushimaJapan
  3. 3.Department of Pathology and Diagnostic PathologyFukushima Medical University School of MedicineFukushimaJapan
  4. 4.Department of PediatricsFukushima Medical University School of MedicineFukushimaJapan
  5. 5.Department of DermatologyFukushima Medical University School of MedicineFukushimaJapan

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