Characterization of a novel human natural killer-cell line (NK-YS) established from natural killer cell lymphoma/leukemia associated with Epstein-Barr virus infection.
A novel cell line was established from a patient with a leukemic-state nasal angiocentric natural killer (NK) cell lymphoma with systemic skin infiltration. The morphology of the leukemic cells was large-granular-lymphocyte (LGL), and their immunophenotype was CD2+, CD3-, CD5+, CD7+, CD16-, CD56+, and CD57-. The presence of Epstein-Barr viral (EBV) genome was shown in specimens from the patient's nose, skin, and peripheral blood by in situ hybridization using an EBV-encoded small RNA-1 probe or by Southern blotting using a terminal-repeat probe of the EBV genome. Leukemic cells were cocultured with a mouse stromal cell line (SPY3-2) in the presence of 100 U/mL recombinant human interleukin-2 and a novel stromal cell-independent cell line, NK-YS, was established. The NK-YS cells showed LGL morphology and expressed surface CD2, CD5, CD7, CD25, CD56, and CD95. The NK-YS cells retained cytotoxicity against K562 and Jurkat cells. A Southern blotting using a terminal-repeat probe of EBV showed that NK-YS and fresh leukemic cells had a clonal EBV genome, whereas the T-cell receptor beta and gamma chain genes of NK-YS were not rearranged. In an immunocytochemical analysis, the NK-YS cells showed a type-II latent infection of EBV. The NK-YS cells preserved the original characteristics of NK cell lymphoma/leukemia and will be a useful tool for the study of biological characteristics of EBV-associated nasal angiocentric NK cell lymphoma/leukemia.
Tsuchiyama
J
J
Second Department of Internal Medicine, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama, Japan.
Yoshino
T
T
Mori
M
M
Kondoh
E
E
Oka
T
T
Akagi
T
T
Hiraki
A
A
Nakayama
H
H
Shibuya
A
A
Ma
Y
Y
Kawabata
T
T
Okada
S
S
Harada
M
M
D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D004279:DNA, Viral / Q000032:analysis; D019309:Epstein-Barr Virus Nuclear Antigens / Q000096:biosynthesis / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D006103:Granuloma, Lethal Midline / Q000473:pathology / Q000821:virology; D006566:Herpesviridae Infections / Q000473:pathology* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D016130:Immunophenotyping; D017403:In Situ Hybridization; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000473:pathology* / Q000821:virology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology* / Q000821:virology; D008230:Lymphomatoid Granulomatosis / Q000473:pathology* / Q000821:virology; D051379:Mice; D009360:Neoplastic Cells, Circulating / Q000276:immunology / Q000473:pathology*; D009669:Nose Neoplasms / Q000473:pathology* / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000821:virology; D014412:Tumor Virus Infections / Q000473:pathology* / Q000821:virology; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000235:genetics
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D004279:DNA, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D007376:Interleukin-2; D012333:RNA, Messenger; D012367:RNA, Viral; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins