| Autor: |
Chen X; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China.; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, United States., Nie Y; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, United States., Xiao H; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, United States.; School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China., Bian Z; School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China., Scarzello AJ; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, United States., Song NY; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, United States., Trivett AL; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, United States., Yang; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, United States., Oppenheim JJ; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, United States. |
| Abstrakt: |
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. |
