Modulation of lytic molecules restrain serial killing in γδ T lymphocytes

Patrick A. Sandoz (), Kyra Kuhnigk, Edina K. Szabo, Sarah Thunberg, Elina Erikson, Niklas Sandström, Quentin Verron, Andreas Brech, Carsten Watzl, Arnika K. Wagner, Evren Alici, Karl-Johan Malmberg, Michael Uhlin and Björn Önfelt ()
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Patrick A. Sandoz: KTH Royal Institute of Technology
Kyra Kuhnigk: Karolinska Institutet, Karolinska University Hospital
Edina K. Szabo: University of Oslo
Sarah Thunberg: KTH Royal Institute of Technology
Elina Erikson: KTH Royal Institute of Technology
Niklas Sandström: KTH Royal Institute of Technology
Quentin Verron: KTH Royal Institute of Technology
Andreas Brech: University of Oslo
Carsten Watzl: TU Dortmund
Arnika K. Wagner: Karolinska Institutet, Karolinska University Hospital
Evren Alici: Karolinska Institutet, Karolinska University Hospital
Karl-Johan Malmberg: Karolinska Institutet, Karolinska University Hospital
Michael Uhlin: Karolinska Institutet
Björn Önfelt: KTH Royal Institute of Technology

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract γδ T cells play a pivotal role in protection against various types of infections and tumours, from early childhood on and throughout life. They consist of several subsets characterised by adaptive and innate-like functions, with Vγ9Vδ2 being the largest subset in human peripheral blood. Although these cells show signs of cytotoxicity, their modus operandi remains poorly understood. Here we explore, using live single-cell imaging, the cytotoxic functions of γδ T cells upon interactions with tumour target cells with high temporal and spatial resolution. While γδ T cell killing is dominated by degranulation, the availability of lytic molecules appears tightly regulated in time and space. In particular, the limited co-occurrence of granzyme B and perforin restrains serial killing of tumour cells by γδ T cells. Thus, our data provide new insights into the cytotoxic arsenal and functions of γδ T cells, which may guide the development of more efficient γδ T cell based adoptive immunotherapies.

Date: 2023
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DOI: 10.1038/s41467-023-41634-7

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