| First Author | Millet I | Year | 1994 |
| Journal | J Immunol | Volume | 152 |
| Issue | 9 | Pages | 4336-46 |
| PubMed ID | 8157957 | Mgi Jnum | J:17702 |
| Mgi Id | MGI:65733 | Doi | 10.4049/jimmunol.152.9.4336 |
| Citation | Millet I, et al. (1994) Differential regulation of lymphotoxin (LT), lymphotoxin-beta (LT-beta), and TNF-alpha in murine T cell clones activated through the TCR. J Immunol 152(9):4336-46 |
| abstractText | The present study demonstrates differential regulation of three members of the TNF family, lymphotoxin (LT), LT-beta, and TNF-alpha, by activated murine T cell clones. We report for the first time that murine T cells transcribe LT-beta mRNA in the absence of any activating signal. Activation through the TCR by anti-CD3 did not increase the accumulation of LT-beta mRNA but did increase the accumulation of two species of TNF-alpha mRNA and three species of LT mRNA. We determined that anti-CD3-activated T cells differ in their regulation of LT, LT-beta, and TNF-alpha at the transcriptional and post-transcriptional levels. Anti-CD3 activation resulted in substantial increases in the extent of transcription of the TNF-alpha and LT genes, although with different rates. LT mRNA accumulation was also post-transcriptionally regulated by anti-CD3. In anti-CD3-activated T cells, the t1/2 of LT mRNA was three to four times longer than that of TNF-alpha mRNA. LT-beta mRNA decayed at a rate similar to that of LT mRNA. We also noted a dramatic difference in the cycloheximide sensitivity of LT, LT-beta, and TNF-alpha mRNAs. Cycloheximide superinduced the accumulation of LT mRNA, but not that of TNF-alpha and LT-beta mRNA, post-transcriptionally. Thus, this study demonstrates dramatic differences in the molecular mechanisms of regulation of LT, LT-beta, and TNF-alpha. It also indicates that LT production is probably the rate-limiting step in the formation of the LT-LT-beta complex. These differences suggest that the reason for the redundancy of LT, LT-beta, and TNF-alpha is their differential regulation rather than their functions. |
