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Two different molecular pathways account for low IL-2 receptor and c-myc mRNA expression by lpr Lyt-2- L3T4- T cells.

K Katagiri, T Katagiri, S Yokota, R A Eisenberg, P L Cohen and J P Ting
J Immunol September 15, 1988, 141 (6) 2145-2152;
K Katagiri
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T Katagiri
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S Yokota
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R A Eisenberg
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P L Cohen
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J P Ting
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Abstract

We have previously shown that Lyt-2- L3T4- T cells from the lymph nodes of MRL/lpr/lpr mice could respond to 12-O-tetradecanoylphorbol-2-acetate (TPA) and A23187 by proliferation, IL-2 secretion, and IL-2R (IL-2R) expression. However, the optimal response was significantly less than that of normal T cells. To understand the molecular mechanisms underlying the relatively inert nature of these cells, the expression of the T cell early competence genes, IL-2R and c-myc, was examined by Northern blot analysis and nuclear run-on assays. In resting lpr Lyt-2- L3T4- T cells, IL-2R mRNA was not detected, whereas the expression of c-myc mRNA was slightly enhanced compared to that of normal T cells. TPA and A23187 synergistically induced both IL-2R and c-myc mRNA expression by the lpr Lyt-2- L3T4- T cells, as well as by normal T cells. However, the amounts of specific mRNA induced in the former were much less than those in the latter. Cycloheximide treatment caused the TPA/A23187-stimulated lpr cells to express large amounts of c-myc mRNA, but not IL-2R mRNA. The deficient expression of c-myc and its correction by cycloheximide treatment were also observed in Con A-stimulated lpr Lyt-2- L3T4- T cells. Run-on transcription assays revealed that the enhancing effect of cycloheximide was most likely at the posttranscriptional level. These findings suggest that two separate mechanisms differentiated by their sensitivity to cycloheximide can inhibit the accumulation of mRNA for early competence genes in lpr Lyt-2- L3T4- T cells. These mechanisms may prevent the full activation of the lpr T cells and lead to abnormal differentiation of these cells.

  • Copyright © 1988 by American Association of Immunologists

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The Journal of Immunology
Vol. 141, Issue 6
15 Sep 1988
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Two different molecular pathways account for low IL-2 receptor and c-myc mRNA expression by lpr Lyt-2- L3T4- T cells.
K Katagiri, T Katagiri, S Yokota, R A Eisenberg, P L Cohen, J P Ting
The Journal of Immunology September 15, 1988, 141 (6) 2145-2152;

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Two different molecular pathways account for low IL-2 receptor and c-myc mRNA expression by lpr Lyt-2- L3T4- T cells.
K Katagiri, T Katagiri, S Yokota, R A Eisenberg, P L Cohen, J P Ting
The Journal of Immunology September 15, 1988, 141 (6) 2145-2152;
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Print ISSN 0022-1767        Online ISSN 1550-6606