Persistence of recipient-derived as well as donor-derived clones of cytomegalovirus pp65-specific cytotoxic T cells long after allogeneic hematopoietic stem cell transplantation

K. Terasako-Saito, H. Nakasone, Y. Tanaka, R. Yamazaki, M. Sato, K. Sakamoto, Y. Ishihara, K. Kawamura, Y. Akahoshi, J. Hayakawa, H. Wada, N. Harada, H. Nakano, K. Kameda, T. Ugai, R. Yamasaki, M. Ashizawa, S. I. Kimura, M. Kikuchi, A. TaniharaJ. Kanda, S. Kako, J. Nishida, Y. Kanda

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3 Citations (Scopus)

Abstract

Background: Cytomegalovirus (CMV)-specific CD8+ cytotoxic T lymphocytes (CMV-CTLs) play a crucial role in preventing CMV disease. However, the actual in vivo dynamics of CMV-CTL clones after allogeneic hematopoietic stem cell transplantation (alloHCT) are still unclear. Methods: Using a single-cell T-cell receptor repertoire analysis, we monitored clones and chimerism of CMV-CTLs in 3 CMV-seropositive alloHCT recipients from CMV-seronegative donors, with or without CMV reactivation. Results: Nearly all of the CMV-CTLs during follow-up were CD45RA-CCR7- effector memory/CD45RA+CCR7- effector T cells, and were highly matured. In each case, the use of BV gene families was restricted, especially in BV5, 7, 28, and 29. Although no common predominant CMV-CTL clones were found, several shared motifs of complementarity-determining region-3 were identified among the 3 cases; QGA in all, TGE and TDT in Case 1 and Case 2, and RDRG in Case 2 and Case 3. In all cases, CMV-CTL clones that were detected for the first time after alloHCT persisted as the dominant clones. In Case 1, without CMV reactivation, recipient-derived CMV-CTLs exclusively persisted as a dominant clone, while all CMV-CTLs in the other 2 cases, with CMV reactivation, were donor derived. Conclusion: Clone monitoring and chimerism analyses should help to further clarify novel aspects of immuno-reconstitution after alloHCT.

Original languageEnglish
Pages (from-to)930-940
Number of pages11
JournalTransplant Infectious Disease
Volume16
Issue number6
DOIs
Publication statusPublished - 2014 Dec 1
Externally publishedYes

Keywords

  • 2402-restricted cytomegalovirus-specific cytotoxic T cells
  • CMV
  • CTL
  • Chimerism analysis
  • Clone monitoring
  • HLA-A
  • Single-cell analysis
  • T cell receptor-β

ASJC Scopus subject areas

  • Infectious Diseases
  • Transplantation

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  • Cite this

    Terasako-Saito, K., Nakasone, H., Tanaka, Y., Yamazaki, R., Sato, M., Sakamoto, K., Ishihara, Y., Kawamura, K., Akahoshi, Y., Hayakawa, J., Wada, H., Harada, N., Nakano, H., Kameda, K., Ugai, T., Yamasaki, R., Ashizawa, M., Kimura, S. I., Kikuchi, M., ... Kanda, Y. (2014). Persistence of recipient-derived as well as donor-derived clones of cytomegalovirus pp65-specific cytotoxic T cells long after allogeneic hematopoietic stem cell transplantation. Transplant Infectious Disease, 16(6), 930-940. https://doi.org/10.1111/tid.12318