Strong sustained IL-2 signal selectively targeted to CD25+ cells dramatically increases sensitivity to LPS-mediated mortality: finding the mechanism
Contractor: Institute of Microbiology of the CAS, v. v. i.
Principal investigator: Kovář Marek
Research years: 2013-2017
Immunocomplexes of IL-2 and certain anti-IL-2 mAb (henceforth IL-2 immunocomplexes) are highly biologically active in vivo. Moreover, it was shown that IL-2 immunocomplexes have selective stimulatory activity for different subsets of IL-2 responsive cells depending on the clone of anti-IL-2 mAb used; thus they can be used for effective modulation of immune system in several different applications. For example, S4B6 mAb/IL-2 immunocomplexes (henceforth IL-2/S4B6) were found to be highly stimulatory for CD122high populations, namely memory CD8+ T cells (CD3+ CD8+ CD44high CD122high) and NK cells (CD3- DX5+ NK1.1+), while only moderate stimulatory activity for Treg cells was found. Conversely, JES6-1A12 mAb/IL-2 immunocomplexes (henceforth IL-2/JES6) vigorously induced expansion of Treg cells (CD4+ CD25+ CD25high) but had no effect on CD122high populations. We noticed that mice treated with IL-2/JES6 immunocomplexes seemed to be more sensitive to LPS. It was unexpected and very surprising finding. Further experiments entirely confirmed this effect of IL-2/JES6 immunocomplexes. The aim of this grant is to elucidate this so far not described novel phenomenon.