Cutting edge: expression of TNFR2 defines a maximally suppressive subset of mouse CD4+CD25+FoxP3+ T regulatory cells: applicability to tumor-infiltrating T regulatory cells.

TNFR2 is predominantly expressed by a subset of human and mouse CD4(+)CD25(+)FoxP3(+) T regulatory cells (Tregs). In this study, we characterized the phenotype and function of TNFR2(+) Tregs in peripheral lymphoid tissues of normal and tumor-bearing C57BL/6 mice. We found that TNFR2 was expressed on 30-40% of the Tregs of the peripheral activated/memory subset that were most highly suppressive. In contrast, TNFR2(-) Tregs exhibited the phenotype of naive cells and only had minimal suppressive activity. Although not typically considered to be Tregs, CD4(+)CD25(-)TNFR2(+) cells nevertheless possessed moderate suppressive activity. Strikingly, the suppressive activity of TNFR2(+) Tregs was considerably more potent than that of reportedly highly suppressive CD103(+) Tregs. In the Lewis lung carcinoma model, more highly suppressive TNFR2(+) Tregs accumulated intratumorally than in the periphery. Thus, TNFR2 identifies a unique subset of mouse Tregs with an activated/memory phenotype and maximal suppressive activity that may account for tumor-infiltrating lymphocyte-mediated immune evasion by tumors.
AuthorsXin Chen, Jeffrey J Subleski, Heather Kopf, O M Zack Howard, Daniela N Männel, Joost J Oppenheim
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 180 Issue 10 Pg. 6467-71 (May 15 2008) ISSN: 0022-1767 [Print] United States
PMID18453563 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD4
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, Tumor Necrosis Factor, Type II
  • Animals
  • Antigens, CD4 (metabolism)
  • Carcinoma, Lewis Lung (immunology)
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors (metabolism)
  • Interleukin-2 Receptor alpha Subunit (metabolism)
  • Lymphocyte Activation (immunology)
  • Lymphocytes, Tumor-Infiltrating (immunology, metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Phenotype
  • Receptors, Tumor Necrosis Factor, Type II (biosynthesis, immunology)
  • T-Lymphocyte Subsets (immunology, metabolism)
  • T-Lymphocytes, Regulatory (immunology, metabolism)
  • Tumor Escape (immunology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: