CD25 Shedding by Human Natural Occurring CD4+CD25+ Regulatory T Cells does not Inhibit the Action of IL‐2

Regulatory T (Treg) cells are important for the maintenance of peripheral tolerance and inhibition of pathogenic T‐cell responses. Therefore, they are important for the limitation of chronic inflammation but can also be deleterious by e.g. limiting antitumour immune responses. Natural occurring Tregs are known to inhibit CD4+ T cell in a contact‐dependent manner, but at the same time, various suppressive factors are secreted. We, here, demonstrate that human naturally occurring CD4+CD25+ Tregs are able to shed large amounts of soluble CD25 upon activation. Secretion of sCD25 could add to the inhibitory effect of Tregs as such secretion in other settings has been proposed to act as a sink for local IL‐2. However, we here demonstrate that supernatant from human Tregs containing high concentration of sCD25 does not inhibit proliferation of CD4+CD25− T cells or inhibit the action of IL‐2 in an in vitro bioassay.

[1]  A. Liston,et al.  Regulatory T Cells , 2011, Methods in Molecular Biology.

[2]  D. Vignali,et al.  How regulatory T cells work , 2008, Nature Reviews Immunology.

[3]  T. Huizinga,et al.  Cutting Edge: TNFR-Shedding by CD4+CD25+ Regulatory T Cells Inhibits the Induction of Inflammatory Mediators1 , 2008, The Journal of Immunology.

[4]  K. Boyd,et al.  The inhibitory cytokine IL-35 contributes to regulatory T-cell function , 2007, Nature.

[5]  E. Gelfand,et al.  Erratum: Naturally occurring lung CD4+CD25+ T cell regulation of airway allergic responses depends on IL-10 induction of TGF-β (Journal of Immunology (2007) 178 (1433-1442)) , 2007 .

[6]  E. Gelfand,et al.  Naturally Occurring Lung CD4+CD25+ T Cell Regulation of Airway Allergic Responses Depends on IL-10 Induction of TGF-β1 , 2007, The Journal of Immunology.

[7]  T. Šarić,et al.  CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms of T-cell inhibition. , 2006, Blood.

[8]  C. Hawrylowicz,et al.  Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma , 2005, Nature Reviews Immunology.

[9]  M. Veldhoen,et al.  CD25+ CD4+ T cells compete with naive CD4+ T cells for IL-2 and exploit it for the induction of IL-10 production. , 2005, International immunology.

[10]  M. Toda,et al.  Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. , 1998, International immunology.

[11]  T. Waldmann,et al.  IL-2Rα on One Cell Can Present IL-2 to IL-2Rβ/γc on Another Cell to Augment IL-2 Signaling , 1998, The Journal of Immunology.

[12]  T. Waldmann,et al.  IL-2R alpha on one cell can present IL-2 to IL-2R beta/gamma(c) on another cell to augment IL-2 signaling. , 1998, Journal of immunology.

[13]  Ethan M. Shevach,et al.  CD4+CD25+ Immunoregulatory T Cells Suppress Polyclonal T Cell Activation In Vitro by Inhibiting Interleukin 2 Production , 1998, The Journal of experimental medicine.

[14]  V. Kronin,et al.  Does the IL-2 receptor alpha chain induced on dendritic cells have a biological function? , 1998, International immunology.

[15]  G. Pizzolo.  The soluble interleukin-2 receptor as a new biological marker in diseases. , 1991, Allergologia et immunopathologia.

[16]  C. Hawkey,et al.  Plasma and tissue interleukin‐2 receptor levels in inflammatory bowel disease , 1990, Clinical and experimental immunology.

[17]  F. Behm,et al.  Serum interleukin 2 receptor levels in childhood acute lymphoblastic leukemia. , 1988, Blood.