Activation-induced cell death in T cell hybridomas is due to apoptosis. Morphologic aspects and DNA fragmentation.
Some T cell hybridomas, upon activation via the TCR, rapidly undergo cell death. In this paper, we demonstrate that this activation-induced cell death (AICD) is accompanied by morphologic changes seen at the electron and light microscopy levels. The most striking changes are an extensive condensation of the chromatin and formation of membrane blebs. In addition to the morphologic changes, a significant portion of genomic DNA is broken at an interval of approximately 200 bp, producing a ladder of oligonucleosome-sized fragments after gel electrophoresis. Taken together, these observations indicate that AICD proceeds via apoptosis, or programmed cell death. This is additionally supported by the observation that AICD-associated phenomena are at least partially inhibited by cycloheximide or actinomycin D. Curiously, AICD and its associated DNA fragmentation are completely inhibited by aurintricarboxylic acid, a known nuclease inhibitor. The possible relationship between AICD in vitro, and the negative selection process (wherein selection may proceed via AICD of developing, autoreactive thymocytes) is discussed.
Department of Immunology, University of Alberta, Edmonton, Canada.
Y F
YF
Shi
M G
MG
Szalay
L
L
Paskar
B M
BM
Sahai
M
M
Boyer
B
B
Singh
D R
DR
Green
D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology; D004249:DNA Damage; D003609:Dactinomycin / Q000494:pharmacology; D006825:Hybridomas / Q000166:cytology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008854:Microscopy, Electron; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D003524:Cyclosporins; D003208:Concanavalin A; D003609:Dactinomycin; D000001:Calcimycin; D001312:Aurintricarboxylic Acid; D012313:RNA; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate