Anti-tumor necrosis factor modulates anti-CD3-triggered T cell cytokine gene expression in vivo

Christiane Ferran, François Dautry, Sylvie Mérite, Katleen Sheehan, Robert Schreiber, Georges Grau, Jean François Bach, Lucienne Chatenoud

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


De novo expression of TNF, IFNγ, IL-3, IL-4, and IL-6 genes was initiated rapidly by treatment of mice with anti-CD3. A specific feature of this reaction was that TNF was derived exclusively from T cells. TNF was produced both as a mature soluble trimeric protein and as a 26-kD anti-TNF-reactive protein compatible with membrane-anchored TNF. Pretreatment with anti-TNF did not affect anti-CD3-triggered TNF mRNA expression in T cells. In contrast, in vivo and in vitro anti-TNF treatment upregulated anti-CD3-induced IFNγ mRNA expression and inhibited IL-4 mRNA expression. These latter effects were not dependent on TNF neutralization: pretreatment with soluble recombinant 55-kD TNF receptor (TBPI) as an alternative TNF-neutralizing agent did not modify the anti-CD3-induced cytokine profile. These results suggest that a direct interaction between anti-TNF and T cell membrane-anchored TNF could account for the observed modulation of cytokine gene expression. The increased expression of INFγ mRNA observed in anti-TNF-treated animals correlated with a decrease in IL-3 and IL-6 mRNA expression. Conversely, IFNγ blockade by a neutralizing anti-IFNγ mAb led to a substantial increase in both IL-3 and IL-6 gene expression induced by anti-CD3. Taken together, these results strongly argue for the existence, in the anti-CD3-induced cytokine cascade, of IFNγ-dependent regulation of IL-3 production, which in turn modulates IL- 6 production.

Original languageEnglish
Pages (from-to)2189-2196
Number of pages8
JournalJournal of Clinical Investigation
Issue number5
StatePublished - May 1994


  • CD3
  • T cell activation
  • cytokines
  • immunosuppression
  • tumor necrosis factor


Dive into the research topics of 'Anti-tumor necrosis factor modulates anti-CD3-triggered T cell cytokine gene expression in vivo'. Together they form a unique fingerprint.

Cite this