Peripheral monitoring of direct and indirect alloantigen presentation pathways in clinical heart transplant recipients

It has been reported that the response to alloantigens presented by the direct and indirect pathway may be of differential relevance after human kidney transplantation. Accordingly, we monitored these routes in peripheral blood mononuclear cells (PBMC) of heart transplant patients from before transplantation and up to 2 years thereafter in an attempt to find a correlation with the clinical status of the patients. Both before and after transplantation, comparable proportions of PBMC samples reacted in mixed lymphocyte culture to nondepleted donor spleen cells (direct route), but never to donor cells depleted for antigen-presenting cells (indirect route). In contrast, the latter route could easily be activated by a nominal antigen and persisted after transplantation, although the proportion of PBMC samples responding was significantly suppressed, irrespective of the occurrence of rejection. Consequently, complete removal of antigen-presenting cells from the stimulator population in a mixed lymphocyte culture with PBMC as responder is not a suitable tool for measuring indirect presentation of alloantigens, and therefore not relevant for monitoring the immunological status of heart transplant recipients.