Abstract
Clonal expansion of antigen-reactive T lymphocytes is driven by the lymphokine interleukin 2 (IL-2). To further elucidate the mechanisms of IL-2 action, we have utilized a differential hybridization procedure to clone IL-2-induced immediate-early genes from an IL-2-stimulated human T-cell cDNA library. To increase the frequency of IL-2-induced transcripts represented in the library, the protein synthesis inhibitor cycloheximide was included during the 2-hr IL-2 stimulation to superinduce gene expression, and the uridine analogue 4-thiouridine was utilized to enable selective purification of newly synthesized transcripts. From the enriched library, we have isolated eight IL-2-induced genes, six of which represent previously unrecognized human sequences. Northern blot analysis revealed that the induction of seven of the genes is specific to the IL-2-mediated G1 "progression" phase of the cell cycle, in that only one gene is also induced during the T-cell receptor-triggered G0-G1 "competence" phase. These results indicate that the effects of IL-2 are mediated by the specific induction of a number of immediate-early genes and provide a means with which to further delineate the mechanisms whereby IL-2 stimulates T-lymphocyte proliferation and differentiation. The methods described in this report should also be of general utility in the dissection of the signaling pathways activated by diverse cytokine receptors.
Original language | English (US) |
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Pages (from-to) | 2719-2723 |
Number of pages | 5 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 90 |
Issue number | 7 |
DOIs | |
State | Published - Apr 1 1993 |
Externally published | Yes |
Keywords
- Cytokine-responsive genes
- Differential cloning
- Human T cells
ASJC Scopus subject areas
- General