title: Engagement of distinct epitopes on CD43 induces different co-stimulatory pathways in human T cells.
abstract: Co-receptors, being either co-stimulatory or co-inhibitory, play a pivotal role in T-cell immunity. Several studies have indicated that CD43, one of the abundant T-cell surface glycoproteins, acts not only as a potent co-receptor but also as a negative regulator for T-cell activation. Here we demonstrate that co-stimulation of human peripheral blood (PB) T cells through two distinct CD43 epitopes recognized by monoclonal antibodies (mAb) CD43-6E5 (T6E5-act) and CD43-10G7 (T10G7-act) potently induced T-cell proliferation. However, T-cell co-stimulation through two CD43 epitopes differentially regulated activation of nuclear factor of activated T cells (NFAT) and nuclear factor-κB (NF-κB) transcription factors, T-cell cytokine production and effector function. T6E5-actproduced high levels of interleukin-22 (IL-22) and interferon-γ (IFN-γ) similar to T cells activated via CD28 (TCD28-act), whereas T10G7-actproduced low levels of inflammatory cytokines but higher levels of regulatory cytokines transforming growth factor-β (TGF-β) and interleukin-35 (IL-35). Compared with T6E5-actor to TCD28-act, T10G7-actperformed poorly in response to re-stimulation and further acquired a T-cell suppressive function. T10G7-actdid not directly inhibit proliferation of responder T cells, but formed stable heterotypic clusters with dendritic cells (DC) via CD2 to constrain activation of responder T cells. Together, our data demonstrate that CD43 is a unique and polarizing regulator of T-cell function.
authors.affiliation: Institute of Immunology, Centre 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, Centre 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, Centre for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Petra
authors.initials: P
authors.lastname: Cejka
authors.affiliation: Institute of Immunology, Centre for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Jutz
authors.affiliation: Institute of Immunology, Centre for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Puck
authors.affiliation: Biopharmaceuticals Research Unit, Inflammation Biology, Novo Nordisk A/S, Måløv, Denmark.
authors.forename: Jens G
authors.initials: JG
authors.lastname: Gerwien
authors.affiliation: Institute of Immunology, Centre 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, Centre 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 Pathophysiology and Immunology, Centre of Molecular Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Herbert
authors.initials: H
authors.lastname: Strobl
authors.affiliation: Institute of Immunology, Centre for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. johannes.stoeckl@meduniwien.ac.at.
authors.forename: Johannes
authors.initials: J
authors.lastname: Stöckl
mesh_terms: D018106:CD28 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D051917:Leukosialin / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D020239:Receptor Cross-Talk; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; D061025:Costimulatory and Inhibitory T-Cell Receptors; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D051917:Leukosialin; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D011948:Receptors, Antigen, T-Cell; C465014:SPN protein, human
keywords: CD43; T-cell polarization; co-stimulation; heterotypic cell adhesion; suppressor T cells