IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-gamma production by CD25(+)Foxp3(-) T cells

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F21%3A00550778" target="_blank" >RIV/61388971:_____/21:00550778 - isvavai.cz</a>
Result on the web
<a href="https://elifesciences.org/articles/62432" target="_blank" >https://elifesciences.org/articles/62432</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.7554/eLife.62432" target="_blank" >10.7554/eLife.62432</a>

Result language
angličtina
Original language name
IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-gamma production by CD25(+)Foxp3(-) T cells
Original language description
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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30102 - Immunology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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