The Potency of Allospecific Tregs Cells Appears to Correlate With T Cell Receptor Functional Avidity

CD4+CD25+ regulatory T cells (Treg cells) are an attractive adoptive cell therapy in mediating transplantation tolerance. T‐cell receptor (TcR) activation is critical for Treg function, suggesting that the TcR avidity of Treg cells used in therapy may affect the therapeutic outcome. To address this, we compared the regulatory capacity of Treg lines expressing TcRs derived from two TcR transgenic mice shown to have the same specificity but different functional avidities. Treg lines generated from CD4+CD25+ T cells from C57BL/6 mice were transduced with one of either of these TcRs. The antigen specificity of the transduced Treg lines was confirmed in vitro. Treg lines expressing the TcR with higher functional avidity showed stronger suppressive capacity in a linked suppression model in vitro. Furthermore, the same Treg lines demonstrated a stronger proliferation in vivo following antigen exposure. Pretreatment of recipient BL/6 mice with these Treg cells, together with anti‐CD8 antibody and Rapamycin therapies, prolonged survival of BALB/c skins, as compared with mice that received Treg lines with lower TcR avidity. Taken together, these data suggest that the TcR functional avidity may be important for Treg function. It highlights the fact that strategies to select Treg with higher functional avidity might be beneficial for immunotherapy in transplantation. Allospecific regulatory T cells with different T cell receptor functional avidity appear to have differential regulatory capacities in graft survival.