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IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-gamma production by CD25(+)Foxp3(-) T cells
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SYSNO ASEP 0550778 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-gamma production by CD25(+)Foxp3(-) T cells Author(s) Tomala, Jakub (MBU-M) RID, ORCID
Weberová, Petra (MBU-M)
Tomalová, Barbora (MBU-M) ORCID
Zákostelská, Zuzana (MBU-M) RID
Sivák, Ladislav (MBU-M) RID
Kovářová, Jiřina (MBU-M)
Kovář, Marek (MBU-M) RID, ORCIDArticle number e62432 Source Title eLife. - : eLife - ISSN 2050-084X
Roč. 10, DEC 21 2021 (2021)Number of pages 22 s. Language eng - English Country GB - United Kingdom Keywords il-2 ; tolerance ; responses ; suppression ; il-2 ; anti-il-2 mab complexes ; cd25 ; T cells ; IFN-gamma ; lps ; hyperreactivity ; Mouse Subject RIV EC - Immunology OECD category Immunology R&D Projects GA13-12885S GA ČR - Czech Science Foundation (CSF) GA18-12973S GA ČR - Czech Science Foundation (CSF) NV19-03-00179 GA MZd - Ministry of Health (MZ) Method of publishing Open access Institutional support MBU-M - RVO:61388971 UT WOS 000733600900001 EID SCOPUS 85122351611 DOI 10.7554/eLife.62432 Annotation Complexes of IL-2 and JES6-1 mAb (IL-2/JES6) provide strong sustained IL-2 signal selective for CD25(+) cells and thus they potently expand T-reg cells. IL-2/JES6 are effective in the treatment of autoimmune diseases and in protecting against rejection of pancreatic islet allografts. However, we found that IL-2/JES6 also dramatically increase sensitivity to LPS-mediated shock in C57BL/6 mice. We demonstrate here that this phenomenon is dependent on endogenous IFN-gamma and T cells, as it is not manifested in IFN-gamma deficient and nude mice, respectively. Administration of IL-2/JES6 leads to the emergence of CD25(+)Foxp3(-)CD4(+) and CD25(+)Foxp3(-)CD8(+) T cells producing IFN-gamma in various organs, particularly in the liver. IL-2/JES6 also increase counts of CD11b(+)CD14(+) cells in the blood and the spleen with higher sensitivity to LPS in terms of TNF-alpha production and induce expression of CD25 in these cells. These findings indicate safety issue for potential use of IL-2/JES6 or similar IL-2-like immunotherapeutics. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2022 Electronic address https://elifesciences.org/articles/62432
Number of the records: 1