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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

eLife

ISSN

2050-084X

e-ISSN

2050-084X

Svazek periodika

10

Číslo periodika v rámci svazku

DEC 21 2021

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

22

Strana od-do

e62432

Kód UT WoS článku

000733600900001

EID výsledku v databázi Scopus

2-s2.0-85122351611