Cytotoxicity against lymphoblastoid cells mediated by a T-cell clone from an aplastic anaemia patient: role of CD59 on target cells.
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 anti-CD3, 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.
Takami
A
A
Third Department of Medicine, Kanazawa University School of Medicine, Kanazawa, Ishikawa, Japan.
Zeng
W
W
Wang
H
H
Matsuda
T
T
Nakao
S
S
D000368:Aged; D000741:Anemia, Aplastic / Q000276:immunology*; D018957:CD59 Antigens / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018957:CD59 Antigens