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Regulatory T cells suppress the formation of super-effector CD8 T cells by limiting IL-2

View ORCID ProfileOksana Tsyklauri, Tereza Chadimova, View ORCID ProfileVeronika Niederlova, Jirina Kovarova, View ORCID ProfileJuraj Michalik, Iva Malatova, View ORCID ProfileSarka Janusova, Helene Rossez, Ales Drobek, Hana Vecerova, Virginie Galati, Marek Kovar, View ORCID ProfileOndrej Stepanek
doi: https://doi.org/10.1101/2021.11.10.467495
Oksana Tsyklauri
1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
2Faculty of Science, Charles University, Prague, Czech Republic
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Tereza Chadimova
1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
2Faculty of Science, Charles University, Prague, Czech Republic
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Veronika Niederlova
1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
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Jirina Kovarova
3Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic
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Juraj Michalik
1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
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Iva Malatova
3Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic
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Sarka Janusova
1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
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Helene Rossez
4Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland
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Ales Drobek
1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
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Hana Vecerova
1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
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Virginie Galati
4Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland
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Marek Kovar
3Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic
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Ondrej Stepanek
1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
4Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland
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  • For correspondence: ondrej.stepanek@img.cas.cz
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Abstract

Regulatory T cells (Tregs) are indispensable for maintaining self-tolerance by suppressing conventional T cells. On the other hand, Tregs may promote tumor growth by inhibiting anti-cancer immunity. In this study, we identified that Tregs increase the quorum of self-reactive CD8+ T cells required for the induction of experimental autoimmune diabetes. Their major suppression mechanism is limiting available IL-2, a key cytokine for activated T cells. Specifically, Tregs inhibit the formation of a previously uncharacterized subset of antigen-stimulated CD8+ T cells. Since these T cells express high levels of IL-7 receptor and cytotoxic molecules (KLRK1, GZMB), and show superior cell killing abilities, we call them super-effector T cells. The administration of agonistic IL-2 immunocomplexes phenocopies the absence of Tregs, i.e., it induces super-effector T cells, promotes autoimmunity, and enhances anti-tumor responses. Counterparts of super-effector T cells were found in the human blood, revealing them as a potential target for immunotherapy.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted November 12, 2021.
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Regulatory T cells suppress the formation of super-effector CD8 T cells by limiting IL-2
Oksana Tsyklauri, Tereza Chadimova, Veronika Niederlova, Jirina Kovarova, Juraj Michalik, Iva Malatova, Sarka Janusova, Helene Rossez, Ales Drobek, Hana Vecerova, Virginie Galati, Marek Kovar, Ondrej Stepanek
bioRxiv 2021.11.10.467495; doi: https://doi.org/10.1101/2021.11.10.467495
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Regulatory T cells suppress the formation of super-effector CD8 T cells by limiting IL-2
Oksana Tsyklauri, Tereza Chadimova, Veronika Niederlova, Jirina Kovarova, Juraj Michalik, Iva Malatova, Sarka Janusova, Helene Rossez, Ales Drobek, Hana Vecerova, Virginie Galati, Marek Kovar, Ondrej Stepanek
bioRxiv 2021.11.10.467495; doi: https://doi.org/10.1101/2021.11.10.467495

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