Active cell migration in retransplanted rat cardiac allografts during the course of chronic rejection

Chronic allograft vasculopathy (CAV) is caused by the infiltration of host immune cells to a graft, but it has been technically difficult to monitor the movements of the cells in graft rejection.

We used a male-specific gene, SRY, as a marker to investigate the dynamics of host cells in a model of CAV in which immunosuppression was unnecessary and anti-male responses were practically negligible. Fluorescent-based real-time quantitative polymerase chain reaction (PCR) was adapted to estimate the fraction of host cells in a graft by the ratio of SRY to IL-2 gene. Using this technique, we studied the turnover and migration of host cells during the course of CAV progression by retransplanting female allografts from male to female or from female to male rats.

We detected histologic CAV 60 days after retransplantation in allografts retransplanted to the F(1) progeny of donor x recipient on the 5th day, but not in those retransplanted on the 3rd day, regardless of the mismatches in the genders. Most of the initial infiltrating cells disappeared rapidly in both cases. The fraction of migrating cells from the second recipient, however, continuously increased in allografts developing CAV, and 60 days after retransplantation exceeded 50%, whereas it stayed at 5% to 15% in those not developing CAV. ED-1-positive macrophages/monocytes were likely candidates for the migrated cells.

We have developed a simple method to measure the migration of host cells into a graft. This technique was useful, at least in certain rat strains, to investigate the cellular mechanisms of chronic cardiac allograft rejection.