Evaluation of cytomegalovirus-specific T-cell reconstitution in patients after various allogeneic haematopoietic stem cell transplantation using interferon-γ-enzyme-linked immunospot and human leucocyte antigen tetramer assays with an immunodominant T-cell epitope

Mutsuko Ohnishi, Toshiharu Sakurai, Yuji Heike, Rie Yamazaki, Yoshinobu Kanda, Yoichi Takaue, Hideaki Mizoguchi, Yutaka Kawakami

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Cytomegalovirus (CMV) infection is a major complication for patients who received allogeneic haematopoietic stem cell transplantation (HSCT). Accurate monitoring of CMV-specific T-cell reconstitution is required for appropriate decision on treatment, such as anti-viral drugs, which have adverse effects. Although human leucocyte antigen (HLA) tetramer and interferon-γ-enzyme- linked immunospot (IFN-γ-ELISPOT) assays have been used to measure CMV-specific T cells, detailed comparison of these assays and kinetics of anti-CMV T-cell reconstitution between reduced-intensity transplantation (RIST) and conventional HSCT has not yet been performed. In this study, we performed prospective comparative monitoring of CMV-specific T cells using HLA tetramer and IFN-γ-ELISPOT assays with a single immunodominant CMV 495 peptide in 28 HLA-A*0201 and 9 HLA-A*0206 patients after various allogeneic HSCTs. The IFN-γ-ELISPOT assay was more sensitive for evaluation of functional T cells than the HLA tetramer assay, and CMV-specific T cells were reconstituted earlier in patients who received RIST without anti-thymocyte globulin (ATG) than those receiving RIST with ATG or conventional HSCT. The threshold level for protection from CMV reactivation was estimated as over 1 × 10 6 cells/l peripheral blood with the IFN-γ-ELISPOT assay. These results demonstrate that the IFN-γ-ELISPOT assay with CMV 495 provides more accurate evaluation on CMV immunity in HLA-A*0201 and -A*0206 patients, and may be useful for determining timing of various treatments.

Original languageEnglish
Pages (from-to)472-479
Number of pages8
JournalBritish Journal of Haematology
Volume131
Issue number4
DOIs
Publication statusPublished - 2005 Nov

Fingerprint

Immunodominant Epitopes
T-Lymphocyte Epitopes
Hematopoietic Stem Cell Transplantation
HLA Antigens
Cytomegalovirus
Interferons
Enzyme-Linked Immunospot Assay
T-Lymphocytes
Enzymes
Antilymphocyte Serum
Transplantation
Interferon-alpha
Cytomegalovirus Infections
Immunity
Peptides

Keywords

  • Cytomegalovirus
  • Haematopoietic stem cell transplantation
  • Human leucocyte antigen tetramer
  • Interferon-γ-enzyme-linked immunospot
  • Reduced-intensity transplantation

ASJC Scopus subject areas

  • Hematology

Cite this

Evaluation of cytomegalovirus-specific T-cell reconstitution in patients after various allogeneic haematopoietic stem cell transplantation using interferon-γ-enzyme-linked immunospot and human leucocyte antigen tetramer assays with an immunodominant T-cell epitope. / Ohnishi, Mutsuko; Sakurai, Toshiharu; Heike, Yuji; Yamazaki, Rie; Kanda, Yoshinobu; Takaue, Yoichi; Mizoguchi, Hideaki; Kawakami, Yutaka.

In: British Journal of Haematology, Vol. 131, No. 4, 11.2005, p. 472-479.

Research output: Contribution to journalArticle

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abstract = "Cytomegalovirus (CMV) infection is a major complication for patients who received allogeneic haematopoietic stem cell transplantation (HSCT). Accurate monitoring of CMV-specific T-cell reconstitution is required for appropriate decision on treatment, such as anti-viral drugs, which have adverse effects. Although human leucocyte antigen (HLA) tetramer and interferon-γ-enzyme- linked immunospot (IFN-γ-ELISPOT) assays have been used to measure CMV-specific T cells, detailed comparison of these assays and kinetics of anti-CMV T-cell reconstitution between reduced-intensity transplantation (RIST) and conventional HSCT has not yet been performed. In this study, we performed prospective comparative monitoring of CMV-specific T cells using HLA tetramer and IFN-γ-ELISPOT assays with a single immunodominant CMV 495 peptide in 28 HLA-A*0201 and 9 HLA-A*0206 patients after various allogeneic HSCTs. The IFN-γ-ELISPOT assay was more sensitive for evaluation of functional T cells than the HLA tetramer assay, and CMV-specific T cells were reconstituted earlier in patients who received RIST without anti-thymocyte globulin (ATG) than those receiving RIST with ATG or conventional HSCT. The threshold level for protection from CMV reactivation was estimated as over 1 × 10 6 cells/l peripheral blood with the IFN-γ-ELISPOT assay. These results demonstrate that the IFN-γ-ELISPOT assay with CMV 495 provides more accurate evaluation on CMV immunity in HLA-A*0201 and -A*0206 patients, and may be useful for determining timing of various treatments.",
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AU - Sakurai, Toshiharu

AU - Heike, Yuji

AU - Yamazaki, Rie

AU - Kanda, Yoshinobu

AU - Takaue, Yoichi

AU - Mizoguchi, Hideaki

AU - Kawakami, Yutaka

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