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Geertje J D van Mierlo, Hans U Scherer, Marjolijn Hameetman, Mary E Morgan, Roelof Flierman, Tom W J Huizinga, René E M Toes, Cutting Edge: TNFR-Shedding by CD4+CD25+ Regulatory T Cells Inhibits the Induction of Inflammatory Mediators, The Journal of Immunology, Volume 180, Issue 5, March 2008, Pages 2747–2751, https://doi.org/10.4049/jimmunol.180.5.2747
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Abstract
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-α 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.