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. 2022 Feb 8;12:790775. doi: 10.3389/fimmu.2021.790775

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Copyright © 2022 Krause, Mengwasser, Phithak, Beato, Appis, Milford, Pratschke, Sauer, Kuehl, Vogel, Goodyear, Hammerich, Tacke, Haas, Müller and Utku

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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(A) Coincubation of humanized TIRC7 agonist antibody significantly induce TIRC7+ IR1 cells in human PBMC cultures after 72h compared to IgG-control ex vivo (n=7). ** mAb = p.0025. (B) Exposure of purified CD25+CD4+ cells to IL-2 plus agonist anti-TIRC7 mAb leads to profound expansion of IR1 cells after 2 weeks. The absolute numbers of purified Treg cells after 2 weeks of expansion cultures are shown. The absolute numbers of IR1 cells in the presence of TIRC7 antibody plus IL-2 exceed those achieved in the IL-2 cultures alone by several fold. (C) Stability of suppressive phenotypes as reflected based on the expression of markers LAP, CD39, GARP, IL-10 and FOXP3 remain high and unchanged in expanded IR1+ cultures after 14 days. (D) In BrdU proliferation assay, expanded human IR1+ cells show more potent inhibition of lymphocyte activation in mixed lymphocyte culture (MLC) compared to IR1neg Tregs.