EXPRESSION OF GRANZYME-A AND PERFORIN IN MOUSE HEART-TRANSPLANTS IMMUNOSUPPRESSED WITH DONOR-SPECIFIC TRANSFUSION AND ANTI-CD4 MONOCLONAL-ANTIBODY

Granzyme A and perforin are produced by activated cytotoxic T lymphocy tes and their expression correlates with the appearance of cytotoxicit y. Using in situ hybridization and immunohistochemistry, we examined t he phenotype of cellular infiltration and the appearance of granzyme A (+) and perform(+) cells in a mouse cardiac transplant model where the recipients were pretreated with donor-specific transfusion, anti-CD4 monoclonal antibody, or both. While the profiles of cellular infiltrat ion failed to correlate with graft survival, tolerized grafts, as comp ared with untreated allografts, showed a decreased frequency of granzy me A and perforin expression. These functional markers of cytotoxic T lymphocytes can differentiate between rejecting and indefinitely survi ving grafts and may be of value in dissecting the immunological events involved in tolerance induction.