Expression of Tcf-1 mRNA and surface TCR-CD3 complexes are reduced during apoptosis of T cells.
When a T cell hybridoma, 70.7, was treated with a Ca2+ ionophore (A23187), apoptotic cell death was induced. Interestingly, we observed that the expression of Tcf-1, a T cell-specific transcription factor, mRNA was reduced by approximately 5-fold in the A23187-treated apoptotic cells compared to an ethanol-treated control. The hybridoma cells, however, did not display such a reduced expression of Tcf-1 mRNA upon treatment with buthionine sulfoxide, which is known to induce a necrosis-like cell death. When another T cell hybridoma, KMIs-8.3.5, was treated with A23187 and phorbol myristate acetate, which leads to activation-induced apoptosis, Tcf-1 expression was again greatly reduced. However, a mutant line (KCIT1-8.5) derived from KMIs-8.3.5, which produces IL-2 upon activation and is resistant to apoptosis, did not show such reduction in Tcf-1 expression. We also showed that the reduced expression level of CD3epsilon mRNA and surface TCR-CD3 complex in apoptotic T cells is caused by the reduced expression of Tcf-1. When 70.7 cells were transfected with a plasmid DNA pSVtcf-1, in which Tcf-1 gene expression is driven by the SV40 promoter, such reduction of the Tcf-1 mRNA and the surface expression of the TCR-CD3 complex were not observed upon apoptosis induction. Our results suggest that the reduced expression of Tcf-1 is specific for the apoptotic, but not for the activating, process of T cells and is also responsible for the reduced surface expression of the TCR-CD3 in apoptotic T cells.
Jeon
S H
SH
Institute for Molecular Biology and Genetics and Department of Molecular Biology, Seoul National University, Korea.
Jeong
S
S
Lee
C
C
Kim
J K
JK
Kim
Y S
YS
Chung
H Y
HY
Park
S D
SD
Seong
R H
RH
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects; D051538:Hepatocyte Nuclear Factor 1-alpha; D006825:Hybridomas / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000096:biosynthesis* / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000187:drug effects; D051822:T Cell Transcription Factor 1; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D012333:RNA, Messenger; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011956:Receptors, Cell Surface; D051822:T Cell Transcription Factor 1; D014157:Transcription Factors; D000001:Calcimycin