Single-cell T-cell receptor-β analysis of HLA-A*2402-restricted CMV- pp65-specific cytotoxic T-cells in allogeneic hematopoietic SCT

H. Nakasone, Y. Tanaka, Rie Yamazaki, K. Terasako, M. Sato, K. Sakamoto, R. Yamasaki, H. Wada, Y. Ishihara, K. Kawamura, T. Machishima, M. Ashizawa, S. I. Kimura, M. Kikuchi, A. Tanihara, J. Kanda, S. Kako, J. Nishida, Y. Kanda

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Cellular immunity is important for the control of CMV infection after allogeneic hematopoietic cell transplantation (Allo-HCT). However, the actual in vivo dynamics of CMV-specific cytotoxic T cell (CMV-CTL) clones are still unclear. We conducted clone monitoring of tetramer + CMV-CTLs in HLA-A*2402-positive donor-patient pairs, using a direct single-cell analysis that enabled the simultaneous identification and quantification of CTL clones. Clone dynamics were assessed in three cases with or without CMV reactivation. In Case-1 without CMV reactivation, despite the long-term use of systemic steroid, dominant clones of Donor-1 persisted and remained dominant. The CMV-CTLs at 1 year after Allo-HCT included a high proportion of CD45RA + CCR7 - effector and CD27 - CD57 + mature T cells. On the other hand, in Cases-2 and -3 with CMV reactivation, novel clones appeared and became dominant during the follow-up. Their CMV-CTLs included more CD27 + immature T cells at 1 year after Allo-HCT. With regard to clonotypes, HLA-A*2402-restricted CMV-CTLs tended to select BV7 and BJ1-1 genes for complementarity-determining region 3 (CDR3) of T-cell receptor (TCR)-β. Specific amino-acid sequences of CDR3 of TCR-β were found in each case. Patterns of clone reconstitution and phenotype would be different according to CMV reactivation. In vivo clone monitoring of CMV-CTLs could provide insight into the mechanism of immunological reconstitution following Allo-HCT.

Original languageEnglish
Pages (from-to)87-94
Number of pages8
JournalBone Marrow Transplantation
Volume49
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1
Externally publishedYes

Fingerprint

HLA-A Antigens
T-Cell Antigen Receptor
Clone Cells
T-Lymphocytes
Cell Transplantation
Complementarity Determining Regions
Tissue Donors
Single-Cell Analysis
Infection Control
Cellular Immunity
Amino Acid Sequence
Steroids
Phenotype

Keywords

  • Clone monitoring
  • HLA-A2402-restricted CMV-specific cytotoxic T cells
  • Single-cell analysis
  • T-cell receptor-b

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Single-cell T-cell receptor-β analysis of HLA-A*2402-restricted CMV- pp65-specific cytotoxic T-cells in allogeneic hematopoietic SCT. / Nakasone, H.; Tanaka, Y.; Yamazaki, Rie; Terasako, K.; Sato, M.; Sakamoto, K.; Yamasaki, R.; Wada, H.; Ishihara, Y.; Kawamura, K.; Machishima, T.; Ashizawa, M.; Kimura, S. I.; Kikuchi, M.; Tanihara, A.; Kanda, J.; Kako, S.; Nishida, J.; Kanda, Y.

In: Bone Marrow Transplantation, Vol. 49, No. 1, 01.01.2014, p. 87-94.

Research output: Contribution to journalArticle

Nakasone, H, Tanaka, Y, Yamazaki, R, Terasako, K, Sato, M, Sakamoto, K, Yamasaki, R, Wada, H, Ishihara, Y, Kawamura, K, Machishima, T, Ashizawa, M, Kimura, SI, Kikuchi, M, Tanihara, A, Kanda, J, Kako, S, Nishida, J & Kanda, Y 2014, 'Single-cell T-cell receptor-β analysis of HLA-A*2402-restricted CMV- pp65-specific cytotoxic T-cells in allogeneic hematopoietic SCT', Bone Marrow Transplantation, vol. 49, no. 1, pp. 87-94. https://doi.org/10.1038/bmt.2013.122
Nakasone, H. ; Tanaka, Y. ; Yamazaki, Rie ; Terasako, K. ; Sato, M. ; Sakamoto, K. ; Yamasaki, R. ; Wada, H. ; Ishihara, Y. ; Kawamura, K. ; Machishima, T. ; Ashizawa, M. ; Kimura, S. I. ; Kikuchi, M. ; Tanihara, A. ; Kanda, J. ; Kako, S. ; Nishida, J. ; Kanda, Y. / Single-cell T-cell receptor-β analysis of HLA-A*2402-restricted CMV- pp65-specific cytotoxic T-cells in allogeneic hematopoietic SCT. In: Bone Marrow Transplantation. 2014 ; Vol. 49, No. 1. pp. 87-94.
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abstract = "Cellular immunity is important for the control of CMV infection after allogeneic hematopoietic cell transplantation (Allo-HCT). However, the actual in vivo dynamics of CMV-specific cytotoxic T cell (CMV-CTL) clones are still unclear. We conducted clone monitoring of tetramer + CMV-CTLs in HLA-A*2402-positive donor-patient pairs, using a direct single-cell analysis that enabled the simultaneous identification and quantification of CTL clones. Clone dynamics were assessed in three cases with or without CMV reactivation. In Case-1 without CMV reactivation, despite the long-term use of systemic steroid, dominant clones of Donor-1 persisted and remained dominant. The CMV-CTLs at 1 year after Allo-HCT included a high proportion of CD45RA + CCR7 - effector and CD27 - CD57 + mature T cells. On the other hand, in Cases-2 and -3 with CMV reactivation, novel clones appeared and became dominant during the follow-up. Their CMV-CTLs included more CD27 + immature T cells at 1 year after Allo-HCT. With regard to clonotypes, HLA-A*2402-restricted CMV-CTLs tended to select BV7 and BJ1-1 genes for complementarity-determining region 3 (CDR3) of T-cell receptor (TCR)-β. Specific amino-acid sequences of CDR3 of TCR-β were found in each case. Patterns of clone reconstitution and phenotype would be different according to CMV reactivation. In vivo clone monitoring of CMV-CTLs could provide insight into the mechanism of immunological reconstitution following Allo-HCT.",
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AU - Terasako, K.

AU - Sato, M.

AU - Sakamoto, K.

AU - Yamasaki, R.

AU - Wada, H.

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