CD161 expression defines new human γδ T cell subsets
Karunathilaka, Amali, Halstrom, Samuel, Price, Patricia, Holt, Michael, Lutzky, Viviana P., Doolan, Denise L., Kupz, Andreas, Bell, Scott C., Thomson, Rachel M., Miles, John J., and Ratnatunga, Champa N. (2022) CD161 expression defines new human γδ T cell subsets. Immunity & Ageing, 19. 11.
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Abstract
γδ T cells are a highly versatile immune lineage involved in host defense and homeostasis, but questions remain around their heterogeneity, precise function and role during health and disease. We used multi−parametric flow cytometry, dimensionality reduction, unsupervised clustering, and self-organizing maps (SOM) to identify novel γδ T cell naïve/memory subsets chiefly defined by CD161 expression levels, a surface membrane receptor that can be activating or suppressive. We used middle-to-old age individuals given immune blockade is commonly used in this population. Whilst most Vδ1+subset cells exhibited a terminal differentiation phenotype, Vδ1− subset cells showed an early memory phenotype. Dimensionality reduction revealed eight γδ T cell clusters chiefly diverging through CD161 expression with CD4 and CD8 expression limited to specific subpopulations. Comparison of matched healthy elderly individuals to bronchiectasis patients revealed elevated Vδ1+ terminally differentiated effector memory cells in patients potentially linking this population with chronic proinflammatory disease.
| Item ID: | 72696 |
|---|---|
| Item Type: | Article (Research - C1) |
| ISSN: | 1742-4933 |
| Keywords: | Bronchiectasis; CD161; Cellular immunity; FlowSOM; High dimensional flow cytometry; Immune checkpoint; Unsupervised clustering; γδ T cell; γδ T cell multifunctionality; γδ T cell subsets |
| Copyright Information: | © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
| Funders: | James Cook University (JCU), National Health and Medical Research Council (NHMRC), QIMRB Medical Research Institute, Australian Institute of Tropical Health and Medicine (AITHM), Rebecca L. Cooper Foundation for Medical Research |
| Projects and Grants: | JCU International Postdoctoral Scholarship, NHMRC Career Development Fellowship 1031652, NHMRC Career Development Fellowship 1131732, NHMRC Principal Research Fellowship 1137285, NHMRC Career Development Fellowship, Rebecca L Cooper Foundation for Medical Research (10509) |
| Date Deposited: | 19 Oct 2022 01:01 |
| FoR Codes: | 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320499 Immunology not elsewhere classified @ 100% |
| SEO Codes: | 20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions @ 100% |
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