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

摘要

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