Deficiency of C5aR prolongs renal allograft survival.

نویسندگان

  • Qijun Li
  • Qi Peng
  • Guolan Xing
  • Ke Li
  • Naiyin Wang
  • Conrad A Farrar
  • Lucy Meader
  • Steven H Sacks
  • Wuding Zhou
چکیده

Interaction between C5a, a product of complement activation, and its receptor (C5aR) upregulates antigen-specific T cell responses by modulating the activation of antigen-presenting cells and T cells. Whether this C5a-C5aR interaction contributes to the immune responses that promote renal allograft rejection is unknown. Here, we found that deficiency of C5aR in both graft and recipient reduced allospecific T cell responses and prolonged renal allograft survival. In addition, lack of C5aR impaired the function of donor and recipient antigen-presenting cells and inhibited the response of recipient T cells to allostimulation. Furthermore, deficiency of C5aR in both graft and recipient reduced early inflammation in the grafts, with less cellular infiltration around the vessels and fewer F4/80 positive cells in the peritubular interstitium. These data demonstrate that C5aR is critical for a full adaptive immune response and mediates renal allograft rejection. Engagement of C5aR on dendritic cells and T cells modulates their function, enhancing allospecific T cell responses that lead to allograft rejection. Targeting C5a signaling may have therapeutic potential for T cell-mediated graft rejection.

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عنوان ژورنال:
  • Journal of the American Society of Nephrology : JASN

دوره 21 8  شماره 

صفحات  -

تاریخ انتشار 2010