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.

• Authors: Xin Chen, Jeffrey J Subleski, Heather Kopf, O M Zack Howard, Daniela N Männel, Joost J Oppenheim
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 180 Issue 10 Pg. 6467-71 (May 15 2008) ISSN: 0022-1767 [Print] United States
• PMID: 18453563 (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

• CD4 Antigens
• Forkhead Transcription Factors
• Foxp3 protein, mouse
• Interleukin-2 Receptor alpha Subunit
• Receptors, Tumor Necrosis Factor, Type II

Topics

• Animals
• CD4 Antigens (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)