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Open Access 01-04-2020 | Anti-CD3 Antibody | Original Article

Suppressive activity of Vδ2⁺ γδ T cells on αβ T cells is licensed by TCR signaling and correlates with signal strength

Authors: Karin Schilbach, Naomi Krickeberg, Carlotta Kaißer, Simon Mingram, Janika Kind, Gabrielle M. Siegers, Hisayoshi Hashimoto

Published in: Cancer Immunology, Immunotherapy | Issue 4/2020

Abstract

Despite recent progress in the understanding of γδ T cells’ roles and functions, their interaction with αβ T cells still remains to be elucidated. In this study, we sought to clarify what precisely endows peripheral Vδ2⁺ T cells with immunosuppressive function on autologous αβ T cells. We found that negatively freshly isolated Vδ2⁺ T cells do not exhibit suppressive behavior, even after stimulation with IL-12/IL-18/IL-15 or the sheer contact with butyrophilin-3A1-expressing tumor cell lines (U251 or SK-Mel-28). On the other hand, Vδ2⁺ T cells positively isolated through TCR crosslinking or after prolonged stimulation with isopentenyl pyrophosphate (IPP) mediate strong inhibitory effects on αβ T cell proliferation. Stimulation with IPP in the presence of IL-15 induces the most robust suppressive phenotype of Vδ2⁺ T cells. This indicates that Vδ2⁺ T cells’ suppressive activity is dependent on a TCR signal and that the degree of suppression correlates with its strength. Vδ2⁺ T cell immunosuppression does not correlate with their Foxp3 expression but rather with their PD-L1 protein expression, evidenced by the massive reduction of suppressive activity when using a blocking antibody. In conclusion, pharmacologic stimulation of Vδ2⁺ T cells via the Vδ2 TCR for activation and expansion induces Vδ2⁺ T cells' potent killer activity while simultaneously licensing them to suppress αβ T cell responses. Taken together, the study is a further step to understand—in more detail—the suppressive activity of Vδ2⁺ γδ T cells.

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Title: Suppressive activity of Vδ2+ γδ T cells on αβ T cells is licensed by TCR signaling and correlates with signal strength
Authors: Karin Schilbach
Naomi Krickeberg
Carlotta Kaißer
Simon Mingram
Janika Kind
Gabrielle M. Siegers
Hisayoshi Hashimoto
Publication date: 01-04-2020
Publisher: Springer Berlin Heidelberg
Keyword: Anti-CD3 Antibody
Published in: Cancer Immunology, Immunotherapy / Issue 4/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-019-02469-8

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