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

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 fo...

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Autores principales: Tomala, Jakub, Weberova, Petra, Tomalova, Barbora, Jiraskova Zakostelska, Zuzana, Sivak, Ladislav, Kovarova, Jirina, Kovar, Marek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8691839/
https://www.ncbi.nlm.nih.gov/pubmed/34932467
http://dx.doi.org/10.7554/eLife.62432
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author Tomala, Jakub
Weberova, Petra
Tomalova, Barbora
Jiraskova Zakostelska, Zuzana
Sivak, Ladislav
Kovarova, Jirina
Kovar, Marek
author_facet Tomala, Jakub
Weberova, Petra
Tomalova, Barbora
Jiraskova Zakostelska, Zuzana
Sivak, Ladislav
Kovarova, Jirina
Kovar, Marek
author_sort Tomala, Jakub
collection PubMed
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-γ and T cells, as it is not manifested in IFN-γ 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-γ 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-α 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.
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spelling pubmed-86918392021-12-22 IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-γ production by CD25(+)Foxp3(-) T cells Tomala, Jakub Weberova, Petra Tomalova, Barbora Jiraskova Zakostelska, Zuzana Sivak, Ladislav Kovarova, Jirina Kovar, Marek eLife Immunology and Inflammation 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-γ and T cells, as it is not manifested in IFN-γ 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-γ 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-α 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. eLife Sciences Publications, Ltd 2021-12-21 /pmc/articles/PMC8691839/ /pubmed/34932467 http://dx.doi.org/10.7554/eLife.62432 Text en © 2021, Tomala et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology and Inflammation
Tomala, Jakub
Weberova, Petra
Tomalova, Barbora
Jiraskova Zakostelska, Zuzana
Sivak, Ladislav
Kovarova, Jirina
Kovar, Marek
IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-γ production by CD25(+)Foxp3(-) T cells
title IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-γ production by CD25(+)Foxp3(-) T cells
title_full IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-γ production by CD25(+)Foxp3(-) T cells
title_fullStr IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-γ production by CD25(+)Foxp3(-) T cells
title_full_unstemmed IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-γ production by CD25(+)Foxp3(-) T cells
title_short IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-γ production by CD25(+)Foxp3(-) T cells
title_sort il-2/jes6-1 mab complexes dramatically increase sensitivity to lps through ifn-γ production by cd25(+)foxp3(-) t cells
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8691839/
https://www.ncbi.nlm.nih.gov/pubmed/34932467
http://dx.doi.org/10.7554/eLife.62432
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