Killer-like receptors and GPR56 progressive expression defines cytokine production of human CD4+ memory T cells

Kim-Long Truong, Stephan Schlickeiser, Katrin Vogt, David Boës, Katarina Stanko, Christine Appelt, Mathias Streitz, Gerald Grütz, Nadja Stobutzki, Christian Meisel, Christina Iwert, Stefan Tomiuk, Julia K. Polansky, Andreas Pascher, Nina Babel, Ulrik Stervbo, Igor Sauer, Undine Gerlach and Birgit Sawitzki ()
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Kim-Long Truong: Institute of Medical Immunology, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Stephan Schlickeiser: Institute of Medical Immunology, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Katrin Vogt: Institute of Medical Immunology, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
David Boës: Institute of Medical Immunology, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Katarina Stanko: Institute of Medical Immunology, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Christine Appelt: Institute of Medical Immunology, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Mathias Streitz: Institute of Medical Immunology, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Gerald Grütz: Institute of Medical Immunology, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Nadja Stobutzki: Institute of Medical Immunology, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Christian Meisel: Institute of Medical Immunology, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Christina Iwert: Institute of Medical Immunology, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Stefan Tomiuk: Milteny Biotec GmbH
Julia K. Polansky: Charité – Universitätsmedizin Berlin
Andreas Pascher: Charité – Universitätsmedizin Berlin
Nina Babel: Charité – Universitätsmedizin Berlin
Ulrik Stervbo: University Clinic of Ruhr-University Bochum
Igor Sauer: Charité – Universitätsmedizin Berlin
Undine Gerlach: Charité – Universitätsmedizin Berlin
Birgit Sawitzki: Institute of Medical Immunology, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract All memory T cells mount an accelerated response on antigen reencounter, but significant functional heterogeneity is present within the respective memory T-cell subsets as defined by CCR7 and CD45RA expression, thereby warranting further stratification. Here we show that several surface markers, including KLRB1, KLRG1, GPR56, and KLRF1, help define low, high, or exhausted cytokine producers within human peripheral and intrahepatic CD4+ memory T-cell populations. Highest simultaneous production of TNF and IFN-γ is observed in KLRB1+KLRG1+GPR56+ CD4 T cells. By contrast, KLRF1 expression is associated with T-cell exhaustion and reduced TNF/IFN-γ production. Lastly, TCRβ repertoire analysis and in vitro differentiation support a regulated, progressive expression for these markers during CD4+ memory T-cell differentiation. Our results thus help refine the classification of human memory T cells to provide insights on inflammatory disease progression and immunotherapy development.

Date: 2019
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DOI: 10.1038/s41467-019-10018-1

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