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 journalArticlepeer-review

25 Citations (Scopus)

Abstract

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
Volume6
DOIs
Publication statusPublished - 7 Sep 2016

Scopus Subject Areas

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