CD161 expression defines new human γδ T cell subsets

gamma delta 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 gamma delta T cell naive/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 V delta 1(+)subset cells exhibited a terminal differentiation phenotype, V delta 1(-) subset cells showed an early memory phenotype. Dimensionality reduction revealed eight gamma delta 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 V delta 1(+) terminally differentiated effector memory cells in patients potentially linking this population with chronic proinflammatory disease.

Automated summary

Gamma delta T cells are a versatile immune lineage involved in host defense and homeostasis. Using various techniques, we identified novel subsets of gamma delta T cells defined by CD161 expression levels. In the elderly population, V delta 1(-) subset cells exhibited an early memory phenotype, while V delta 1(+) subset cells showed a terminal differentiation phenotype. The clustering of gamma delta T cells was mainly determined by CD161 expression, with limited expression of CD4 and CD8 in specific subpopulations. Comparison between healthy elderly individuals and patients with bronchiectasis revealed elevated levels of V delta 1(+) terminally differentiated effector memory cells in patients, potentially linking this population with chronic proinflammatory disease.