gamma-ray irradiation induces B7.1 expression in myeloid leukaemic cells.
Expression of B7 molecules provides co-stimulatory signals to T lymphocytes, which prevent the induction of anergy. It has been previously reported that B7.1 gene transfer in a murine leukaemia model induced a potent antileukaemic immunity and that relative expression of B7.1 and B7.2 in human acute myeloid leukaemia (AML) had prognostic significance. As ex vivo engineering of leukaemic cells for immunotherapy protocols would require prior irradiation of these cells before reinjection to the patient, we investigated in murine and leukaemic cell lines and in 20 ex vivo primary cultured acute myeloid leukaemic cells the effect of gamma-irradiation on the expression of B7 molecules. We observed that gamma-irradiation enhanced B7.1 molecule expression in murine leukaemic cell lines and in B7.2 molecules in human HL60 and K562 cell lines. gamma-Irradiation induced B7.1 molecule expression in 90% AML samples but only 21% showed B7.2 molecule expression enhancement. B7.1 expression was increased both at the protein and RNA level in human AML cells but only at the protein level in the DA1-3b murine cell line. Oxidative stress increased B7.1 expression in the murine DA1-3b cell line but human cell lines and AML samples remained unaffected both by heat shock and oxidative stress, suggesting different pathways of B7.1 induction between mouse and human cells. Our data show that B7.1 expression can be induced by ex vivo irradiation of AML cells, indicating that these cells can express co-stimulatory molecules without gene transfer.
Vereecque
R
R
Unité INSERM 124, IRCL, Lille, and Service des maladies du sang, CHU Lille, France.
Buffenoir
G
G
Gonzalez
R
R
Cambier
N
N
Hetuin
D
D
Bauters
F
F
Fenaux
P
P
Quesnel
B
B
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D051940:B7-2 Antigen; D015152:Blotting, Northern; D002460:Cell Line; D002478:Cells, Cultured / Q000528:radiation effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger