NKG2 D blockade attenuated cardiac allograft vasculopathy in a mouse model of cardiac transplantation.

A previous paper has reported that blockade of NKG2 D was effective in protecting allograft in murine models of cardiac transplantation, but the mechanism of NKG2 D blockade on attenuated cardiac allograft vasculopathy ( CAV) was still unknown. In our current study, we found that wild-type recipients treated with anti- NKG2 D monoclonal antibody (m Ab) 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- Ig plus anti- NKG2 D m Ab-treated recipients, whereas IL-17 had no significant effect on allograft survival and CAV grade in CTLA-4- Ig plus anti- NKG2 D m Ab-treated recipients. Furthermore, the prolonged allograft survival induced by NKG2 D blockade was abrogated partially with depletion of regulatory T cells. In conclusion, blockade of NKG2 D combined with CTLA-4- Ig attenuated CAV and this effect was associated with lower alloantibody production, inhibited IL-6 expression and enhanced expansion of regulatory T cells. [ABSTRACT FROM AUTHOR]