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

Author:

Tomala Jakub1ORCID,Weberova Petra1,Tomalova Barbora1,Jiraskova Zakostelska Zuzana2,Sivak Ladislav1ORCID,Kovarova Jirina1,Kovar Marek1ORCID

Affiliation:

1. Laboratory of Tumor Immunology, Institute of Microbiology, Czech Academy of Sciences

2. Laboratory of Cellular and Molecular Immunology, Institute of Microbiology, Czech Academy of Sciences

Abstract

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.

Funder

Czech Science Foundation

Institutional Research Concept RVO

Ministry of Health of the Czech Republic

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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