Characterization of lpr-derived T cell hybridomas: Fas-deficient hybridomas are deathless, growth-arrested, and cytotoxic upon activation.
T cell hybridomas that are deathless upon TCR crosslinking were generated from lpr mice. The deathless hybridomas (1.4 and 5D5) expressed extremely low Fas even after anti-CD3 activation, whereas activation-induced cell death (AICD) was observed for Fas-expressing hybridomas. The deathless hybridomas were activated to produce FasL and IL-2, indicating that the intrinsic defect in Fas expression or up-regulation resulted in AICD blockade. The deathless hybridoma cells expressed longer and stronger FasL cytotoxicity than AICD-sensitive hybridomas. Although deathless, activated 5D5 cells were arrested at the G1/S border. Growth arrest lasted for at least 5 days, but some cells eventually recovered and proliferated. The deathless 5D5 cells were used to demonstrate that AICD includes a fratricidal mechanism that kills AICD-sensitive bystanders. The deathless T cell hybridomas are useful tools for studying T cell activation-dependent functions sensitive to AICD.
Cui
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H
Arthritis Center, Boston University School of Medicine, Massachusetts, USA.
el-Khatib
M
M
Sherr
D H
DH
Ettinger
R
R
Sy
M S
MS
Marshak-Rothstein
A
A
Ju
S T
ST
D000818:Animals; D001483:Base Sequence; D016923:Cell Death; D002455:Cell Division; D017931:DNA Primers / Q000737:chemistry; D053222:Fas Ligand Protein; D015870:Gene Expression; D006825:Hybridomas / Q000473:pathology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology*; D019014:fas Receptor / Q000502:physiology*
D017931:DNA Primers; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor