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Tissue Distribution Dynamics of Human NK Cells Inferred from Peripheral Blood Depletion Kinetics after Sphingosine-1-Phosphate Receptor Blockade

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Mehling Matthias, Burgener Anne-Valérie, Brinkmann Volmar, Bantug Glenn, Dimeloe Sarah, Hoenger Gideon, Kappos Ludwig, Hess Christoph,
Project Metabolic and functional signature of senescent CD8+ T cells
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Original article (peer-reviewed)

Journal Scandinavian Journal of immunology
Volume (Issue) 82(5)
Page(s) 460 - 466
Title of proceedings Scandinavian Journal of immunology
DOI 10.1111/sji.12347

Abstract

Human natural killer (NK) cell subsets differentially distribute throughout the organism. While CD56dim and CD56bright NK cell subsets similarly reside in the bone marrow (BM), the CD56dim population predominantly accumulates in non-lymphoid tissues and the CD56bright counterpart in lymphoid tissue (LT). The dynamics with which these NK cell subsets redistribute to tissues remains unexplored. Here, we studied individuals newly exposed to fingolimod, a drug that efficiently blocks sphingosine-1-phosphate (S1P)-directed lymphocyte – including NK cell – egress from tissue to blood. During an observation period of 6h peripheral blood depletion of CD56bright NK cells was observed 3 h after first dose of fingolimod, with 40–50% depletion after 6 h, while a decrease of the numbers of CD56dim NK cells did not reach the level of statistical significance. In vitro, CD56bright and CD56dim NK cells responded comparably to the BM-homing chemokine CXCL12, while CD56bright NK cells migrated more efficiently in gradients of the LT-homing chemokines CCL19 and CCL21. In conjuncture with these in vitro studies, the indirectly observed subset-specific depletion kinetics from blood are compatible with preferential and more rapid redistribution of CD56bright NK cells from blood to peripheral tissue such as LT and possibly also the inflamed central nervous system. These data shed light on an unexplored level at which access of NK cells to LT, and thus, for example antigen-presenting cells, is regulated.
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