Possible involvement of allogeneic antigens recognised by donor-derived CD4 + cytotoxic T cells in selective GVL effects after stem cell transplantation of patients with haematological malignancy

Maiko Matsushita, Rie Yamazaki, Hideyuki Ikeda, Takehiko Mori, Hidetoshi Sumimoto, Tomonobu Fujita, Shinichiro Okamoto, Yasuo Ikeda, Yutaka Kawakami

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Abstract

Cytotoxic T lymphocyte (CTL) lines specific for allogeneic antigens were generated by in vitro stimulation of donor-derived peripheral blood mononuclear cells obtained from patients who received human leucocyte antigen (HLA)-matched allogeneic haematopoietic stem cell transplantation (HSCT). One of the allogeneic antigen-specific CD4 + CTL lines, CTL-A, generated from a patient with T cell acute lymphoblastic leukaemia, recognised HLA-DPB1*0501-positive Epstein-Barr virus-immortalised human B cell line (EBV-B cells), phytohaemagglutinin blasts and leukaemia cells, but not interferon-γ (IFN-γ) treated HLA-DPB1*0501-positive fibroblasts, indicating that this CD4 + T-cell line recognised a minor histocompatibility antigen (mHa) that is preferentially expressed in haematopoietic cells in an HLA-DPB1*0501-restricted manner. The other CD4 + CTL line, CTL-B, generated from a patient with chronic myeloid leukaemia, recognised mismatched HLA-DQB1*0303 on EBV-B cells and phytohaemagglutinin (PHA) blasts. Interestingly, this CTL line did not recognise IFN-γ-treated recipient's skin fibroblasts, as HLA-DQ was merely upregulated even after IFN-γ stimulation in non-haematopoietic cells including fibroblasts, endothelial cells and hepatocytes. These results suggest that these CD4 positive CTLs, specific for mismatch HLA-DQ and mHa that are preferentially expressed on haematopoietic cells, may play an important role in induction of selective graft-versus-leukaemia effect without development of graft-versus-host disease after allogeneic HSCT.

Original languageEnglish
Pages (from-to)56-65
Number of pages10
JournalBritish Journal of Haematology
Volume132
Issue number1
DOIs
Publication statusPublished - 2006 Jan

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Stem Cell Transplantation
Hematologic Neoplasms
HLA Antigens
Cytotoxic T-Lymphocytes
Tissue Donors
T-Lymphocytes
Antigens
Minor Histocompatibility Antigens
Interferons
Fibroblasts
Hematopoietic Stem Cell Transplantation
Phytohemagglutinins
Human Herpesvirus 4
Cell Line
Leukemia
B-Lymphocytes
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
CD4 Antigens
Graft vs Host Disease
Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Keywords

  • CD4 cytotoxic T cells
  • Graft-versus leukaemia effect
  • Minor histocompatibility antigens
  • Stem cell transplantation

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "Possible involvement of allogeneic antigens recognised by donor-derived CD4 + cytotoxic T cells in selective GVL effects after stem cell transplantation of patients with haematological malignancy",
abstract = "Cytotoxic T lymphocyte (CTL) lines specific for allogeneic antigens were generated by in vitro stimulation of donor-derived peripheral blood mononuclear cells obtained from patients who received human leucocyte antigen (HLA)-matched allogeneic haematopoietic stem cell transplantation (HSCT). One of the allogeneic antigen-specific CD4 + CTL lines, CTL-A, generated from a patient with T cell acute lymphoblastic leukaemia, recognised HLA-DPB1*0501-positive Epstein-Barr virus-immortalised human B cell line (EBV-B cells), phytohaemagglutinin blasts and leukaemia cells, but not interferon-γ (IFN-γ) treated HLA-DPB1*0501-positive fibroblasts, indicating that this CD4 + T-cell line recognised a minor histocompatibility antigen (mHa) that is preferentially expressed in haematopoietic cells in an HLA-DPB1*0501-restricted manner. The other CD4 + CTL line, CTL-B, generated from a patient with chronic myeloid leukaemia, recognised mismatched HLA-DQB1*0303 on EBV-B cells and phytohaemagglutinin (PHA) blasts. Interestingly, this CTL line did not recognise IFN-γ-treated recipient's skin fibroblasts, as HLA-DQ was merely upregulated even after IFN-γ stimulation in non-haematopoietic cells including fibroblasts, endothelial cells and hepatocytes. These results suggest that these CD4 positive CTLs, specific for mismatch HLA-DQ and mHa that are preferentially expressed on haematopoietic cells, may play an important role in induction of selective graft-versus-leukaemia effect without development of graft-versus-host disease after allogeneic HSCT.",
keywords = "CD4 cytotoxic T cells, Graft-versus leukaemia effect, Minor histocompatibility antigens, Stem cell transplantation",
author = "Maiko Matsushita and Rie Yamazaki and Hideyuki Ikeda and Takehiko Mori and Hidetoshi Sumimoto and Tomonobu Fujita and Shinichiro Okamoto and Yasuo Ikeda and Yutaka Kawakami",
year = "2006",
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doi = "10.1111/j.1365-2141.2005.05843.x",
language = "English",
volume = "132",
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T1 - Possible involvement of allogeneic antigens recognised by donor-derived CD4 + cytotoxic T cells in selective GVL effects after stem cell transplantation of patients with haematological malignancy

AU - Matsushita, Maiko

AU - Yamazaki, Rie

AU - Ikeda, Hideyuki

AU - Mori, Takehiko

AU - Sumimoto, Hidetoshi

AU - Fujita, Tomonobu

AU - Okamoto, Shinichiro

AU - Ikeda, Yasuo

AU - Kawakami, Yutaka

PY - 2006/1

Y1 - 2006/1

N2 - Cytotoxic T lymphocyte (CTL) lines specific for allogeneic antigens were generated by in vitro stimulation of donor-derived peripheral blood mononuclear cells obtained from patients who received human leucocyte antigen (HLA)-matched allogeneic haematopoietic stem cell transplantation (HSCT). One of the allogeneic antigen-specific CD4 + CTL lines, CTL-A, generated from a patient with T cell acute lymphoblastic leukaemia, recognised HLA-DPB1*0501-positive Epstein-Barr virus-immortalised human B cell line (EBV-B cells), phytohaemagglutinin blasts and leukaemia cells, but not interferon-γ (IFN-γ) treated HLA-DPB1*0501-positive fibroblasts, indicating that this CD4 + T-cell line recognised a minor histocompatibility antigen (mHa) that is preferentially expressed in haematopoietic cells in an HLA-DPB1*0501-restricted manner. The other CD4 + CTL line, CTL-B, generated from a patient with chronic myeloid leukaemia, recognised mismatched HLA-DQB1*0303 on EBV-B cells and phytohaemagglutinin (PHA) blasts. Interestingly, this CTL line did not recognise IFN-γ-treated recipient's skin fibroblasts, as HLA-DQ was merely upregulated even after IFN-γ stimulation in non-haematopoietic cells including fibroblasts, endothelial cells and hepatocytes. These results suggest that these CD4 positive CTLs, specific for mismatch HLA-DQ and mHa that are preferentially expressed on haematopoietic cells, may play an important role in induction of selective graft-versus-leukaemia effect without development of graft-versus-host disease after allogeneic HSCT.

AB - Cytotoxic T lymphocyte (CTL) lines specific for allogeneic antigens were generated by in vitro stimulation of donor-derived peripheral blood mononuclear cells obtained from patients who received human leucocyte antigen (HLA)-matched allogeneic haematopoietic stem cell transplantation (HSCT). One of the allogeneic antigen-specific CD4 + CTL lines, CTL-A, generated from a patient with T cell acute lymphoblastic leukaemia, recognised HLA-DPB1*0501-positive Epstein-Barr virus-immortalised human B cell line (EBV-B cells), phytohaemagglutinin blasts and leukaemia cells, but not interferon-γ (IFN-γ) treated HLA-DPB1*0501-positive fibroblasts, indicating that this CD4 + T-cell line recognised a minor histocompatibility antigen (mHa) that is preferentially expressed in haematopoietic cells in an HLA-DPB1*0501-restricted manner. The other CD4 + CTL line, CTL-B, generated from a patient with chronic myeloid leukaemia, recognised mismatched HLA-DQB1*0303 on EBV-B cells and phytohaemagglutinin (PHA) blasts. Interestingly, this CTL line did not recognise IFN-γ-treated recipient's skin fibroblasts, as HLA-DQ was merely upregulated even after IFN-γ stimulation in non-haematopoietic cells including fibroblasts, endothelial cells and hepatocytes. These results suggest that these CD4 positive CTLs, specific for mismatch HLA-DQ and mHa that are preferentially expressed on haematopoietic cells, may play an important role in induction of selective graft-versus-leukaemia effect without development of graft-versus-host disease after allogeneic HSCT.

KW - CD4 cytotoxic T cells

KW - Graft-versus leukaemia effect

KW - Minor histocompatibility antigens

KW - Stem cell transplantation

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