NKG 2 D blockade attenuated cardiac allograft vasculopathy in a mouse model of cardiac transplantation

Summary A previous paper has reported that blockade of NKG 2 D was effective in protecting allograft in murine models of cardiac transplantation, but the mechanism of NKG 2 D blockade on attenuated cardiac allograft vasculopathy ( CAV ) was still unknown. In our current study, we found that wild‐type recipients treated with anti‐ NKG 2 D monoclonal antibody (m A b) plus cytotoxic T lymphocyte antigen ( CTLA)‐ 4‐immunoglobulin ( I) g showed prolonged allograft survivals (>90 days, P  < 0·001) significantly and attenuated CAV . These in‐vivo results correlated with reduced alloantibody production, low expression of interleukin ( IL) ‐17 and IL ‐6, while infiltration of regulatory T cells increased. IL ‐6 administration induced shorter allograft survival and higher CAV grade in CTLA‐ 4– I g plus anti‐ NKG 2 D m A b‐treated recipients, whereas IL ‐17 had no significant effect on allograft survival and CAV grade in CTLA‐ 4– I g plus anti‐ NKG 2 D m A b‐treated recipients. Furthermore, the prolonged allograft survival induced by NKG 2 D blockade was abrogated partially with depletion of regulatory T cells. In conclusion, blockade of NKG 2 D combined with CTLA‐ 4– I g attenuated CAV and this effect was associated with lower alloantibody production, inhibited IL ‐6 expression and enhanced expansion of regulatory T cells.