Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1784618832115007488 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8691839 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT tomalajakub il2jes61mabcomplexesdramaticallyincreasesensitivitytolpsthroughifngproductionbycd25foxp3tcells AT weberovapetra il2jes61mabcomplexesdramaticallyincreasesensitivitytolpsthroughifngproductionbycd25foxp3tcells AT tomalovabarbora il2jes61mabcomplexesdramaticallyincreasesensitivitytolpsthroughifngproductionbycd25foxp3tcells AT jiraskovazakostelskazuzana il2jes61mabcomplexesdramaticallyincreasesensitivitytolpsthroughifngproductionbycd25foxp3tcells AT sivakladislav il2jes61mabcomplexesdramaticallyincreasesensitivitytolpsthroughifngproductionbycd25foxp3tcells AT kovarovajirina il2jes61mabcomplexesdramaticallyincreasesensitivitytolpsthroughifngproductionbycd25foxp3tcells AT kovarmarek il2jes61mabcomplexesdramaticallyincreasesensitivitytolpsthroughifngproductionbycd25foxp3tcells |