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Regulation of T lymphocyte proliferation. Interleukin 2-mediated induction of c-myb gene expression is dependent on T lymphocyte activation state.
- Source :
-
The Journal of experimental medicine [J Exp Med] 1989 Jul 01; Vol. 170 (1), pp. 105-21. - Publication Year :
- 1989
-
Abstract
- We previously reported that with time, after antigenic stimulation of antigen-regulated murine T lymphocyte clones, total IL-2-R expression decayed 10-50-fold, commensurate with a decline in the ability of the cells to proliferate to IL-2. However, late after antigenic stimulation, when the cells were refractory to the IL-2-proliferative stimulus, high levels of high affinity IL-2-R remained. In this report we further explore the basis of unresponsiveness to IL-2 in the quiescent clones. We show that the proto-oncogene c-myc is induced in the late cell population by IL-2 to comparable levels observed early after antigen stimulation. IL-2-dependent c-myb induction, however, is seen only early after activation but not in the late-activated population. Analysis of the IL-2-dependent expression of c-myb mRNA with time after antigenic stimulation showed that steadystate c-myb expression declines dramatically with kinetics closely paralleling a decay in IL-2-dependent proliferative ability. In contrast, steadystate c-myc expression remains high throughout this period. Expression of c-myb is critical for proliferation of these cells since antisense oligodeoxy-nucleotide to c-myb can inhibit their IL-2-dependent proliferation. We present evidence for a pathway of c-myb induction via the TCR that is independent of the IL-2/IL-2-R interaction. In addition, the inhibition of IL-2-R-induced c-myb expression by 2-aminopurine and enhanced induction of c-myb via the TCR demonstrate that TCR activation and IL-2-R activation lead to induction of c-myb by different mechanisms.
- Subjects :
- Animals
Base Sequence
Cells, Cultured
Clone Cells
DNA Probes
Interleukin-2 metabolism
Kinetics
Mice
Mice, Inbred Strains
Molecular Sequence Data
Proto-Oncogene Proteins c-myb
Receptors, Interleukin-2 immunology
Transcription, Genetic
Interleukin-2 pharmacology
Lymphocyte Activation
Proto-Oncogene Proteins genetics
Proto-Oncogenes drug effects
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1007
- Volume :
- 170
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 2664066
- Full Text :
- https://doi.org/10.1084/jem.170.1.105