Epstein–Barr virus‐specific T‐cell cytotoxicity is mediated through the perforin pathway in patients with lymphoproliferative disorders after allogeneic bone marrow transplantation

• Ayami Yoshimi

• Ikuya Tsuge

• Hiroe Namizaki

• Yo Hoshino

• Hiroshi Kimura

• Yoshiyuki Takahashi

• Nobuhiro Watanabe

• Kiyotaka Kuzushima

• Seiji Kojima

Abstract

Summary. The in vivo cytotoxic mechanism of Epstein–Barr virus (EBV)‐specific cytotoxic lymphocytes was examined in a patient who suffered with EBV‐associated lymphoproliferative disease (LPD) after bone marrow transplantation (BMT). His peripheral CD8 + T‐cell count was significantly increased and > 70% of these cells were EBV‐specific by fluorescence‐activated cell sorter (FACS) analysis for interferon‐γ production. Intracellular perforin expression was markedly increased in CD8 + T cells by FACS analysis. The lymphocytes from this patient had cytotoxic activity against autologous EBV + lymphoblastoid cell lines which were completely inhibited by concanamycin A, an inhibitor of perforin, and a anti‐human leucocyte antigen (HLA)‐class I monoclonal antibody. These results suggest that the cytotoxicity was mediated by the perforin, in an HLA‐class I‐restricted manner. We performed serial intracellular perforin analyses in another patient who also showed endogenous expansion of EBV‐specific CD8 + T cells that coincided with an increased EBV‐DNA load. Perforin expression in the CD8 + and CD4 + T cells paralleled the EBV‐specific CD8 + T cells and EBV‐DNA load, which also suggests that perforin mediates EBV‐specific cytolysis in vivo and is responsible for effective immunosurveillance against EBV reactivation after BMT. Evaluation of host immunity against EBV by determining perforin expression in lymphocytes and EBV‐specific lymphocytes along with quantification of EBV‐DNA may be useful for predicting the clinical course of patients with EBV‐associated LPD after BMT.

Journal

• British Journal of Haematology

  British Journal of Haematology 116 (3), 710-715, 2002-03

  Wiley

Keywords

• Hematology

Details

• CRID: 1364233268615082112
• NII Article ID: 30014736429
• DOI: 10.1046/j.0007-1048.2001.03299.x
• ISSN: 13652141
• ISSN: 00071048
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.0007-1048.2001.03299.x
• Web Site: https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.0007-1048.2001.03299.x
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