Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Modak, M; Majdic, O; Cejka, P; Jutz, S; Puck, A; Gerwien, JG; Steinberger, P; Zlabinger, GJ; Strobl, H; Stöckl, J.
Engagement of distinct epitopes on CD43 induces different co-stimulatory pathways in human T cells.
Immunology. 2016; 149(3):280-296
Doi: 10.1111/imm.12642
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- Co-Autor*innen der Med Uni Graz
- Strobl Herbert
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- 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-act produced high levels of interleukin-22 (IL-22) and interferon-γ (IFN-γ) similar to T cells activated via CD28 (TCD28-act ), whereas T10G7-act produced 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-act or to TCD28-act , T10G7-act performed poorly in response to re-stimulation and further acquired a T-cell suppressive function. T10G7-act did 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. © 2016 The Authors. Immunology Published by John Wiley & Sons Ltd.
- Find related publications in this database (using NLM MeSH Indexing)
- CD28 Antigens - metabolism
- Cell Differentiation -
- Cells, Cultured -
- Costimulatory and Inhibitory T-Cell Receptors - metabolism
- Cytokines - metabolism
- Dendritic Cells - immunology
- Epitopes, T-Lymphocyte - metabolism
- Humans -
- Immune Tolerance -
- Leukosialin - immunology
- Leukosialin - metabolism
- NF-kappa B - metabolism
- NFATC Transcription Factors - metabolism
- Receptor Cross-Talk -
- Receptors, Antigen, T-Cell - metabolism
- Signal Transduction -
- T-Lymphocyte Subsets - immunology
- T-Lymphocytes, Regulatory - immunology
- Find related publications in this database (Keywords)
- CD43
- co-stimulation
- heterotypic cell adhesion
- suppressor T cells
- T-cell polarization