title: The soluble cytoplasmic tail of CD45 (ct-CD45) in human plasma contributes to keep T cells in a quiescent state.
abstract: The cytoplasmic tail of CD45 (ct-CD45) is proteolytically cleaved and released upon activation of human phagocytes. It acts on T cells as an inhibitory, cytokine-like factor in vitro. Here, we show that ct-CD45 is abundant in human peripheral blood plasma from healthy adults compared with plasma derived from umbilical cord blood and plasma from patients with rheumatoid arthritis or systemic lupus erythematosus. Plasma depleted of ct-CD45 enhanced T-cell proliferation, while addition of exogenous ct-CD45 protein inhibited proliferation and reduced cytokine production of human T lymphocytes in response to TCR signaling. Inhibition of T-cell proliferation by ct-CD45 was overcome by costimulation via CD28. T-cell activation in the presence of ct-CD45 was associated with an upregulation of the quiescence factors Schlafen family member 12 (SLFN12) and Krueppel-like factor 2 (KLF2) as well as of the cyclin-dependent kinase (CDK) inhibitor p27kip1. In contrast, positive regulators of the cell cycle such as cyclin D2 and D3 as well as CDK2 and CDK4 were found to be downregulated in response to ct-CD45. In summary, we demonstrate that ct-CD45 is present in human plasma and sets the threshold of T-cell activation.
authors.affiliation: Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Puck
authors.affiliation: Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hopf
authors.affiliation: Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Madhura
authors.initials: M
authors.lastname: Modak
authors.affiliation: Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Otto
authors.initials: O
authors.lastname: Majdic
authors.affiliation: Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Petra
authors.initials: P
authors.lastname: Cejka
authors.affiliation: Department for Rheumatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Stephan
authors.initials: S
authors.lastname: Blüml
authors.affiliation: Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schmetterer
authors.affiliation: Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Catharina
authors.initials: C
authors.lastname: Arnold-Schrauf
authors.affiliation: Novo Nordisk A/S, Biopharmaceuticals Research Unit, Måløv, Denmark.
authors.forename: Jens G
authors.initials: JG
authors.lastname: Gerwien
authors.affiliation: Novo Nordisk A/S, Biopharmaceuticals Research Unit, Måløv, Denmark.
authors.forename: Klaus S
authors.initials: KS
authors.lastname: Frederiksen
authors.affiliation: Department for Gynecology, St. Josef Hospital, Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Thell
authors.affiliation: Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Judith
authors.initials: J
authors.lastname: Leitner
authors.affiliation: Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Steinberger
authors.affiliation: Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Regina
authors.initials: R
authors.lastname: Aigner
authors.affiliation: Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Seyerl-Jiresch
authors.affiliation: Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Zlabinger
authors.affiliation: Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Stöckl
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D056747:Immunomodulation; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000097:blood* / Q000737:chemistry; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D000072417:Protein Domains; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D017493:Leukocyte Common Antigens
keywords: CD45; Immunoregulation; Quiescence; SLFN12; T-cell activation