Cytotoxicity against lymphoblastoid cells mediated by a T-cell clone from an aplastic anaemia patient: Role of CD59 on target cells

Akiyoshi Takami, Weihua Zeng, Hongbo Wang, Tamotsu Matsuda, Shinji Nakao

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24 Scopus citations

Abstract

In an attempt to elucidate the pathogenic role of a CD4+ cytotoxic T- cell clone NT4.2 isolated from the bone marrow of a patient with cyclosporine-dependent aplastic anaemia, we characterized the T-cell clone as well as its cytotoxicity against an autologous Epstein-Barr (EB) virus- transformed B-lymphoblastoid cell line (LCL). NT4-2 expressed BV21+ BJ2.7+ with a complementarity-determining region (CDR) 3 motif of SQGQGEVEQY which was homologous to that of a T-cell clone isolated from a patient with connective tissue disease. NT4.2 started to lyse LCL cells within 2 h and exerted maximal cytotoxicity within 3 h of incubation. The cytotoxicity required the presence of divalent cations and was not associated with DNA fragmentation of the target cells. Anti-CD59 monoclonal antibodies (MoAb) blocked the cytotoxicity to the same degree as antiCD3, HLA-DR or CD2 mAb. Flow cytometric analysis of the peripheral blood of this patient during remission after cyclosporine therapy revealed 1.7% of granulocytes to be deficient in CD59. These findings indicate that NT4.2 exerts its cytotoxicity through a perforin-mediated pathway, not a Fas/Fas ligand-dependent pathway, and that haemopoietic stem cells lacking CD59 may evade cytotoxic T lymphocytes, leading to the in vivo expansion of a paroxysmal nocturnal haemoglobinuria clone.

Original languageEnglish (US)
Pages (from-to)791-796
Number of pages6
JournalBritish journal of haematology
Volume107
Issue number4
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Keywords

  • Aplastic anaemia
  • CD59
  • CTL
  • PNH
  • Perforin-mediated pathway

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