Cutting Edge: TNFR-Shedding by CD4+CD25+ Regulatory T Cells Inhibits the Induction of Inflammatory Mediators

• Published in: The Journal of immunology (1950) Vol. 180; no. 5; pp. 2747 - 2751
• Main Authors: van Mierlo, Geertje J. D, Scherer, Hans U, Hameetman, Marjolijn, Morgan, Mary E, Flierman, Roelof, Huizinga, Tom W. J, Toes, Rene E. M
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-03-2008
• Subjects: Acute-Phase Proteins - antagonists & inhibitors; Acute-Phase Proteins - metabolism; Animals; Cells, Cultured; Humans; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - metabolism; Interleukin-2 Receptor alpha Subunit - biosynthesis; Interleukin-2 Receptor alpha Subunit - metabolism; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - biosynthesis; Lipopolysaccharides - administration & dosage; Lipopolysaccharides - antagonists & inhibitors; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Tumor Necrosis Factor - metabolism; Receptors, Tumor Necrosis Factor, Type I - antagonists & inhibitors; Receptors, Tumor Necrosis Factor, Type I - biosynthesis; Receptors, Tumor Necrosis Factor, Type I - metabolism; Receptors, Tumor Necrosis Factor, Type II - biosynthesis; Receptors, Tumor Necrosis Factor, Type II - deficiency; Receptors, Tumor Necrosis Factor, Type II - physiology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - transplantation; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.180.5.2747

CD4+CD25+ regulatory T (Treg) cells play an essential role in maintaining tolerance to self and nonself. In several models of T cell-mediated (auto) immunity, Treg cells exert protective effects by the inhibition of pathogenic T cell responses. In addition, Treg cells can modulate T cell-independent inflammation. We now show that CD4+CD25+ Treg cells are able to shed large amounts of TNFRII. This is paralleled by their ability to inhibit the action of TNF-alpha both in vitro and in vivo. In vivo, Treg cells suppressed IL-6 production in response to LPS injection in mice. In contrast, Treg cells from TNFRII-deficient mice were unable to do so despite their unhampered capacity to suppress T cell proliferation in a conventional in vitro suppression assay. Thus, shedding of TNFRII represents a novel mechanism by which Treg cells can inhibit the action of TNF, a pivotal cytokine driving inflammation.