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

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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.

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Authors and Affiliations

  1. Department of Transfusion Medicine and Transplantation Immunology, Fukushima Medical University School of Medicine, 1 Hikariga-oka, Fukushima, Fukushima, 960-1295, Japan

    Alain M. Ngoma, Kazuhiko Ikeda, Hiroshi Takahashi, Syunnichi Saito, Kenneth E. Nollet & Hitoshi Ohto

  2. Department of Cardiology and Hematology, Fukushima Medical University School of Medicine, Fukushima, Japan

    Kazuhiko Ikeda, Hiroshi Takahashi, Hayato Matsumoto, Hideyoshi Noji & Kazuei Ogawa

  3. Department of Pathology and Diagnostic Pathology, Fukushima Medical University School of Medicine, Fukushima, Japan

    Yuko Hashimoto & Masafumi Abe

  4. Department of Pediatrics, Fukushima Medical University School of Medicine, Fukushima, Japan

    Kazuhiro Mochizuki, Hideki Sano & Atsushi Kikuta

  5. Department of Dermatology, Fukushima Medical University School of Medicine, Fukushima, Japan

    Mikio Ohtsuka

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  1. Alain M. Ngoma
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Correspondence to Kazuhiko Ikeda.

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Ngoma, A.M., Ikeda, K., Hashimoto, Y. et al. Impaired regulatory T cell reconstitution in patients with acute graft-versus-host disease and cytomegalovirus infection after allogeneic bone marrow transplantation. Int J Hematol 95, 86–94 (2012). https://doi.org/10.1007/s12185-011-0976-7

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  • DOI: https://doi.org/10.1007/s12185-011-0976-7

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