CD28 Superagonist D665-mediated activation of mouse regulatory T cells maintains their phenotype without loss of suppressive quality

Wagner, Johanna; Leicht, Svenja; Hofmann, Manuela; Seifert, F.; Gahn, Sabine; Germer, Christoph‐Thomas; Beyersdorf, Niklas; Otto, Christoph; Klein, Ingo

doi:10.1016/j.imbio.2021.152144

Cited by 1 publication

(2 citation statements)

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“…On day 0, before G3c administration, D665 induced a robust expansion of T reg cells over Teff cells (Fig. 1B), consistent with previous reports (22)(23)(24)(25). The GITR expression was significantly up-regulated on the surface of both T reg and Teff cells (Fig.…”

Section: Induction Of Tr1 Cells In Vivosupporting

confidence: 90%

“…CD28 superagonist bivalently binds to the laterally exposed C″D loop of the extracellular Ig-like domains of the CD28 homodimer and forms a stable lattice on the T cell membrane, which provides strong activating signals and leads to potent polyclonal T cell expansion (4,5,37). The CD28 superagonist D665 has been shown to preferentially expand T reg cells over Teff cells in various rodent models for T reg -based interference with autoimmune and inflammatory disease (22)(23)(24)(25). We also observed robust T reg cell expansion consistent with previously published data (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Combinations of anti-GITR antibody and CD28 superagonist induce permanent allograft acceptance by generating type 1 regulatory T cells

Que

et al. 2022

Sci. Adv.

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Type 1 regulatory T (Tr1) cells represent a subset of IL-10–producing CD4 + Foxp3 − T cells and play key roles in promoting transplant tolerance. However, no effective pharmacological approaches have been able to induce Tr1 cells in vivo. We herein report the combined use of a CD28 superagonist (D665) and anti–glucocorticoid-induced tumor necrosis factor receptor–related protein monoclonal antibody (G3c) to induce Tr1 cells in vivo. Large amounts of IL-10/interferon-γ–co-producing CD4 + Foxp3 − Tr1 cells were generated by D665-G3c sequential treatment in mice. Mechanistic studies suggested that D665-G3c induced Tr1 cells via transcription factors Prdm1 and Maf . G3c contributed to Tr1 cell generation via the activation of mitogen-activated protein kinase–signal transducer and activator of transcription 3 signaling. Tr1 cells suppressed dendritic cell maturation and T cell responses and mediated permanent allograft acceptance in fully major histocompatibility complex–mismatched mice in an IL-10–dependent manner. In vivo Tr1 cell induction is a promising strategy for achieving transplant tolerance.

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Section: Induction Of Tr1 Cells In Vivosupporting

confidence: 90%