Radiation kills human peripheral T cells by a Fas-independent mechanism.
The mechanism by which radiation induces human peripheral T cell apoptosis is not known. We examined sequential changes in post-irradiated peripheral blood mononuclear cells (PBMC(S)) taken from normal volunteers, by using flow-cytometer and an anti-CD3 monoclonal antibody, annexin V, propidium iodide, anti-Fas antibody, and anti-Fas ligand antibody. After 5 or 10 Gy of irradiation with a 60Co radiation therapy unit, most of the human peripheral T cells showed positivity against annexin V in 15 h, and positivity against propidium iodide in 23 h after irradiation. On a microscopy-video system, approximately 80% of mononuclear cells revealed apoptotic changes in 24 h after irradiation. Because of its proposed role in activation-induced cytotoxicity, we also examined the Fas (CD95/Apo-1) pathway in killing T cells by irradiation. Irradiated PBMC, displayed no increase in surface Fas expression and caspase-3 activity relative to non-irradiated cells. In addition, the anti-Fas ligand failed to eliminate the apoptotic death of PBMC, after irradiation. These results suggest that irradiation induces direct apoptosis of T cells by a Fas-independent mechanism.
Ogawa
Y
Y
Department of Radiology, Kochi Medical School, Okoh-cho, Nankoku-shi, Kochi-Prefecture 783-8505, Japan.
Nishioka
A
A
Inomata
T
T
Yoshida
S
S
Nakayama
K I
KI
Kataoka
S
S
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008853:Microscopy / Q000379:methods; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D014741:Video Recording; D019014:fas Receptor / Q000096:biosynthesis*
D000911:Antibodies, Monoclonal; D053222:Fas Ligand Protein; D019014:fas Receptor; D053148:Caspase 3