The Journal of Immunology, Vol 152, Issue 9 4336-4346, Copyright © 1994 by American Association of Immunologists

ARTICLES

Differential regulation of lymphotoxin (LT), lymphotoxin-beta (LT- beta), and TNF-alpha in murine T cell clones activated through the TCR

I Millet and NH Ruddle
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520.

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.

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