S. Kitagawa-sakakida et al., Active cell migration in retransplanted rat cardiac allografts during the course of chronic rejection, J HEART LUN, 19(6), 2000, pp. 584-590
Background: Chronic allograft vasculopathy (CAV) is caused by the infiltrat
ion of host immune cells to a graft, but it has been technically difficult
to monitor the movements of the cells in graft rejection.
Methods: 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 unn
ecessary and anti-male responses were practically negligible. Fluorescent-b
ased 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 c
ells during the course of CAV progression by retransplanting female allogra
fts from male to female or from female to male rats.
Results: We detected histologic CAV 60 days after retransplantation in allo
grafts retransplanted to the F-1 progeny of donor x recipient on the 5th da
y, but not in those retransplanted on the 3rd day, regardless of the mismat
ches in the genders. Most: of the initial infiltrating cells disappeared ra
pidly in both cases. The fraction of migrating cells from the second recipi
ent, however, continuously increased in allografts developing CAV, and 60 d
ays 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.
Conclusions: 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 allogra
ft rejection.