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RNAseq data from: A novel TNFR2 agonist antibody expands highly potent regulatory T cells

Citation

Kuhtreiber, Willem (2020), RNAseq data from: A novel TNFR2 agonist antibody expands highly potent regulatory T cells, Dryad, Dataset, https://doi.org/10.5061/dryad.wh70rxwkj

Abstract

Patients suffering from inflammatory diseases may benefit by enhancing the function of immunosuppressive regulatory T cells (Tregs). Tumor necrosis factor receptor 2 (TNFR2) has emerged as a central control switch on Tregs for maintaining and restoring the immune balance.  Here, we characterized a new human TNFR2-directed antibody agonist.  We found that the antibody agonist expands Tregs with a cellular phenotype and mechanistic properties of maximally suppressive Tregs. RNA-sequencing and metabolite data showed that the antibody induced the expression of genes associated with anti-inflammatory metabolic programs and included increased itaconate levels associated with potent Tregs. Epitope mapping of antibody binding to TNFR2 suggested a possible natural crosslinking surface state that results in stronger intracellular signaling as measured by pathway target gene expression. Notably, Treg expansion was independent of the antibody Fc region, suggesting the antibody will have less toxicity in vivo. Additionally, Treg expansion was not increased by either supplemental ligand (TNF) or by addition of a cross-linking reagent, both indicative of the agonist alone achieving maximal activity, confirmed by an increase in the secretion of soluble TNFR2. Together, these features indicate that the TNFR2 antibody agonist has the potential to safely and effectively treat organ rejection, autoimmunity, graft-versus-host disease, neuroinflammatory disease, and other inflammatory disorders.

Methods

Isolated human CD4 cells were cultured for 10 hours in the presence of IL2 only or IL-2 and agonist antibody. The cells were then washed with PBS, total RNA isolated and processed for RNAseq on NextSeq flow cells.