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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.

Abstract
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
Topics
  • 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)

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