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 Treg cells. IL-2/JES6 are effective in the treatment of autoimmune diseases and in protecting against rejection of pancreatic islet allografts. However, we found...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/62432 |
| _version_ | 1811199886325972992 |
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| author | Jakub Tomala Petra Weberova Barbora Tomalova Zuzana Jiraskova Zakostelska Ladislav Sivak Jirina Kovarova Marek Kovar |
| author_facet | Jakub Tomala Petra Weberova Barbora Tomalova Zuzana Jiraskova Zakostelska Ladislav Sivak Jirina Kovarova Marek Kovar |
| author_sort | Jakub Tomala |
| collection | DOAJ |
| 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 Treg 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. |
| first_indexed | 2024-04-12T01:55:08Z |
| format | Article |
| id | doaj.art-ba46fe21f6f442f593d162462e122627 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:55:08Z |
| publishDate | 2021-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ba46fe21f6f442f593d162462e1226272022-12-22T03:52:49ZengeLife Sciences Publications LtdeLife2050-084X2021-12-011010.7554/eLife.62432IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-γ production by CD25+Foxp3- T cellsJakub Tomala0https://orcid.org/0000-0002-6315-2832Petra Weberova1Barbora Tomalova2Zuzana Jiraskova Zakostelska3Ladislav Sivak4https://orcid.org/0000-0003-2623-8458Jirina Kovarova5Marek Kovar6https://orcid.org/0000-0002-6602-1678Laboratory of Tumor Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czech RepublicLaboratory of Tumor Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czech RepublicLaboratory of Tumor Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czech RepublicLaboratory of Cellular and Molecular Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czech RepublicLaboratory of Tumor Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czech RepublicLaboratory of Tumor Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czech RepublicLaboratory of Tumor Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czech RepublicComplexes 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 Treg 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.https://elifesciences.org/articles/62432il-2/anti-il-2 mab complexesCD25T cellsIFN-γLPShyperreactivity |
| spellingShingle | Jakub Tomala Petra Weberova Barbora Tomalova Zuzana Jiraskova Zakostelska Ladislav Sivak Jirina Kovarova Marek Kovar IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-γ production by CD25+Foxp3- T cells eLife il-2/anti-il-2 mab complexes CD25 T cells IFN-γ LPS hyperreactivity |
| 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 | il-2/anti-il-2 mab complexes CD25 T cells IFN-γ LPS hyperreactivity |
| url | https://elifesciences.org/articles/62432 |
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