MIP-1a, rantes, and IP-10 chemokine expression is associated with T-Cell infiltration during cardiac allograft rejection

We hypothesized that chemokines are pivital molecules for the recruitment of leukocytes during graft rejection. To explore this idea we examined the expression of chemokines in the C57B1/6 to Balb/c heterotopic heart allograft transplant model. Histologkal scores indicated that mild rejection was observed as early as day 3, moderate on day 5 and severe on day 7 in allografted hearts. Immunohistochemical staining (ISH) indicated that CD4 and CDS positive T cells were present as early as day 3 and steadily increased in numbers on days 5 and 7 in the allografted hearts but were rarely observed in isografts. ISH staining for chemokines paralleled the observations of mononuclear infiltration. In allograft tissue, MIP-la, MIP-lb, and RANTES, all potent chemoattractants for monocytes and T cells, were detected as early as day 3 but the number of positive cells was greatly increased on days 5 and 7. RT-PCR on isolated RNA showed that MIP-lb, RANTES and IP-10 were expressed in allografted hearts on days 3, 5 and 7 but were not expressed in native hearts and isografts on any days; MCP-1 was detected in some but not all isografts on days 1, 3 and 5. Our data indicates MIP-la, MIP-lb, and RANTES chemokine expression is correlated with, and perhaps responsible for, T cell and mononuclear infiltration during the early stages of allograft rejection.