Mapping human natural killer cell development in pediatric tonsil by imaging mass cytometry and high-resolution microscopy

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Natural killer (NK) cells develop from CD34+ progenitors in a stage-specific manner defined by changes in cell surface receptor expression and function. Secondary lymphoid tissues, including tonsil, are sites of human NK cell development. Here we present new insights into human NK cell development in pediatric tonsil using cyclic immunofluorescence and imaging mass cytometry. We show that NK cell subset localization and interactions are dependent on NK cell developmental stage and tissue residency. NK cell progenitors are found in the interfollicular domain in proximity to cytokine-expressing stromal cells that promote proliferation and maturation. Mature NK cells are primarily found in the T-cell rich parafollicular domain engaging in cell-cell interactions that differ depending on their stage and tissue residency. The presence of local inflammation results in changes in NK cell interactions, abundance, and localization. This study provides the first comprehensive atlas of human NK cell development in secondary lymphoid tissue.

Authors 14

1. Everardo Hegewisch-Solloa

   Columbia University Irving Medical Center

   Affiliation as printed

   Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York NY 10032

   Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York NY 0032

2. Janine E. Melsen Aachen Department of Immunology, Leiden University Medical Center Laboratory for Pediatric Immunology

   Leiden University Medical Center · Willem-Alexander Kinderziekenhuis

   Affiliation as printed

   Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands

   Laboratory for Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands

   Laboratory for Pediatric Immunology, Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden, The Netherlands

3. Hiranmayi Ravichandran

   Weill Cornell Medicine

   Affiliation as printed

   Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA

   Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, New York, NY, 10065

4. André F. Rendeiro

   Austrian Academy of Sciences · CeMM Research Center for Molecular Medicine · Weill Cornell Medicine

   Affiliation as printed

   Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA

   CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT 25.3, 1090, Vienna, Austria

   Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, New York, NY, 10065

5. Aharon G. Freud

   The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · The Ohio State University

   Affiliation as printed

   Department of Pathology, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210

   Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210

   Department of Pathology, The Ohio State University, Columbus, OH 43210, USA

6. Bethany L. Mundy-Bosse

   The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · The Ohio State University

   Affiliation as printed

   Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210

   Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210

   Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA

7. Johannes C. Melms

   Columbia University Irving Medical Center · Columbia University

   Affiliation as printed

   Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, 10032

   Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, 10032

   Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, 032

8. Shira Esther Eisman

   Columbia University Irving Medical Center

   Affiliation as printed

   Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York NY 10032

   Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York NY 0032

9. Benjamin Izar

   Columbia University Irving Medical Center · Herbert Irving Comprehensive Cancer Center · Columbia University

   Affiliation as printed

   Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, 10032

   Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, 10032

   Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, 10032

   Program for Mathematical Genomics, Columbia University, New York, NY, 10032

   Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, 032

10. Eli Grunstein

    Columbia University Irving Medical Center · Columbia University

    Affiliation as printed

    Department of Otolaryngology - Head and Neck Surgery, Columbia University Medical Center, New York, New York 10032

11. Thomas J. Connors

    Columbia University Irving Medical Center · Columbia University

    Affiliation as printed

    Department of Pediatrics, Division of Pediatric Critical Care and Hospital Medicine, Columbia University Irving Medical Center, New York, NY 10024

12. Olivier Elemento

    Weill Cornell Medicine

    Affiliation as printed

    Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, 10065

13. Amir Horowitz

    Tisch Cancer Institute · Icahn School of Medicine at Mount Sinai

    Affiliation as printed

    Department of Oncological Sciences, Precision Immunology Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029

14. Emily Margaret Mace corresponding

    Columbia University Irving Medical Center

    Affiliation as printed

    Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York NY 10032

    Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York NY 0032