TNFR2 expression by CD4 effector T cells is required to induce full-fledged experimental colitis

Xin Chen*, Yingjie Nie, Haitao XIAO, Zhaoxiang BIAN, Anthony J. Scarzello, Na Young Song, Trivett L. Anna, De Yang, Joost J. Oppenheim

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

38 Citations (Scopus)


There is now compelling evidence that TNFR2 is constitutively expressed on CD4 + Foxp3 + regulatory T cells (Tregs) and TNF-TNFR2 interaction is critical for the activation, expansion and functional stability of Tregs. However, we showed that the expression of TNFR2 was also up-regulated on CD4 + Foxp3 - effector T cells (Teffs) upon TCR stimulation. In order to define the role of TNFR2 in the pathogenic CD4 T cells, we compared the effect of transferred naïve CD4 cells from WT mice and TNFR2 -/- mice into Rag 1 -/- recipients. Transfer of TNFR2-deficient Teff cells failed to induce full-fledged colitis, unlike WT Teffs. This was due to defective proliferative expansion of TNFR2-deficient Teff cells in the lymphopenic mice, as well as their reduced capacity to express proinflammatory Th1 cytokine on a per cell basis. In vitro, the proliferative response of TNFR2 deficient naïve CD4 cells to anti-CD3 stimulation was markedly decreased as compared with that of WT naïve CD4 cells. The hypoproliferative response of TNFR2-deficient Teff cells to TCR stimulation was associated with an increased ratio of p100/p52, providing a mechanistic basis for our findings. Therefore, this study clearly indicates that TNFR2 is important for the proliferative expansion of pathogenic Teff cells.

Original languageEnglish
Article number32834
JournalScientific Reports
Publication statusPublished - 7 Sept 2016

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