CD161 expression defines new human γδ T cell subsets

Immunity & Ageing

Andreas Kupz¹  Denise L. Doolan¹  Amali Karunathilaka²  Champa N. Ratnatunga³  Rachel M. Thomson⁴  Viviana P. Lutzky⁵  John J. Miles⁶  Samuel Halstrom⁷  Patricia Price⁷  Michael Holt⁸  Scott C. Bell⁹ 

[1] Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia;Centre for Molecular Therapeutics, James Cook University, Cairns, Queensland, Australia;Department of Microbiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka;Department of Microbiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka;QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia;Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia;Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia;Gallipoli Medical Research Foundation, Brisbane, Queensland, Australia;Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia;QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia;QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia;Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia;Centre for Molecular Therapeutics, James Cook University, Cairns, Queensland, Australia;Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia;Division of Infection and Immunity, Cardiff University School of Medicine; Systems Immunity Research Institute, Cardiff University, Cardiff, UK;School of Medicine, Curtin University, Western Australia, Australia;The Prince Charles Hospital, Brisbane, Queensland, Australia;Gallipoli Medical Research Foundation, Brisbane, Queensland, Australia;The Prince Charles Hospital, Brisbane, Queensland, Australia;QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia;

关键词: Cellular immunity;    CD161;    γδ T cell;    γδ T cell subsets;    γδ T cell multifunctionality;    High dimensional flow cytometry;    Unsupervised clustering;    FlowSOM;    Immune checkpoint;    Bronchiectasis;   

DOI  :  10.1186/s12979-022-00269-w

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY