Indirect presentation of antigen-coupled cells mediates specific CD4+ T cell tolerance by PD-L1 for the prevention of type 1 diabetes (BA14P.207)

Abstract

Abstract Antigen coupled to the surface of cells using ethylene carbodiimide is a potent inducer of tolerance in multiple models of autoimmunity including Type 1 Diabetes (T1D). Yet, the mechanisms contributing to the induction of T cell tolerance in vivo during T1D are unclear. We used the BDC2.5 T cell receptor transgenic T cell transfer model to study how p31-coupled cells inhibit T cell function in vivo. Antigen-coupled cells that were either deficient in MHC class II or MHC-mismatched induced tolerance similarly to MHC class II-sufficient matched cells, suggesting that indirect presentation of coupled cell antigens is required for tolerance induction in vivo. We also show that BDC2.5 T cells predominantly encounter coupled cell antigen that has been ingested by host antigen presenting cells, and that the inhibitory receptor PD-L1 is required on the host but not the coupled cells to induce tolerance, further highlighting an indirect mechanism of tolerance induction. These data add to our current understanding of how antigen-coupled cells induce tolerance and aid in the translation of this therapeutic into the clinic.