Lack of TNFR2 expression by CD4(+) T cells exacerbates experimental colitis

Eur J Immunol. 2009 Jul;39(7):1743-53. doi: 10.1002/eji.200839132.


TNF plays fundamental roles in the induction and perpetuation of inflammation. The effects of TNF are mediated through TNF receptor (TNFR) 1 or 2. As these two receptors mediate different functions, selective targeting of one receptor may represent a more specific treatment for inflammatory disorders than the complete blocking of TNF. TNFR2 expression is up-regulated in inflammatory bowel disease. Hence, we directly assessed the role of TNFR2 signaling in the CD4(+) T-cell transfer model of colitis using TNFR2(-/-) or WT mice as donors of colitogenic CD4(+)CD45RB(hi) T cells for transfer into syngeneic RAG2(-/-) or RAG2(-/-)TNFR2(-/-) recipient mice. Although the absence of TNFR2 expression by non-lymphoid cells of the recipient mice does not influence the course of colitis, transfer of TNFR2(-/-) CD4(+) T cells leads to an accelerated onset of disease and to more severe signs of inflammation. The enhanced colitogenic potential of TNFR2(-/-) CD4(+) T cells is associated with reduced activation-induced cell death, resulting in an increased accumulation of TNFR2(-/-) CD4(+) T cells. Hence, TNFR2 signaling is crucial for the TNF-dependent contraction of the disease-inducing T cells. Therefore, a selective blocking of TNFR2 may lead to exacerbation rather than attenuation of T-cell-mediated inflammatory disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer / methods
  • Animals
  • Apoptosis
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / transplantation
  • Cell Differentiation
  • Cell Proliferation
  • Colitis / genetics
  • Colitis / metabolism*
  • Colitis / therapy
  • Colon / immunology
  • Colon / metabolism
  • Colon / pathology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Flow Cytometry
  • Gene Expression
  • Interferon-gamma / genetics
  • Interleukin-17 / genetics
  • Interleukin-4 / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Tumor Necrosis Factor, Type II / genetics
  • Receptors, Tumor Necrosis Factor, Type II / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / genetics


  • DNA-Binding Proteins
  • Interleukin-17
  • Rag2 protein, mouse
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Interferon-gamma