Title | Mapping human natural killer cell development in pediatric tonsil by imaging mass cytometry and high-resolution microscopy. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Hegewisch-Solloa E, Melsen JE, Ravichandran H, Rendeiro AF, Freud AG, Mundy-Bosse B, Melms JC, Eisman SE, Izar B, Grunstein E, Connors TJ, Elemento O, Horowitz A, Mace EM |
Journal | bioRxiv |
Date Published | 2023 Sep 06 |
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. |
DOI | 10.1101/2023.09.05.556371 |
Alternate Journal | bioRxiv |
PubMed ID | 37732282 |
PubMed Central ID | PMC10508773 |
Grant List | R37 CA258829 / CA / NCI NIH HHS / United States T32 CA203702 / CA / NCI NIH HHS / United States R01 AI137073 / AI / NIAID NIH HHS / United States R01 CA266446 / CA / NCI NIH HHS / United States F31 AI164869 / AI / NIAID NIH HHS / United States |