期刊
ELIFE
卷 10, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.62432
关键词
il-2; anti-il-2 mab complexes; CD25; T cells; IFN-gamma; LPS; hyperreactivity; Mouse
类别
资金
- Czech Science Foundation [13-12885S, 18-12973S]
- Ministry of Health of the Czech Republic [NV19-03-00179]
- [RVO 61388971]
The IL-2 and JES6-1 mAb complexes selectively expand CD25(+) cells and T-reg cells, but also increase sensitivity to LPS shock in mice, potentially raising safety concerns for their use in immunotherapy.
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.
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