Early detection of acute allograft rejection in rat heart transplantation: flowcytometric monitoring of interleukin 2 receptor expression on CD8 positive lymphocytes.

To assess the usefulness of flowcytometric monitoring in the early detection of acute allograft rejection, we studied surface markers of graft infiltrating lymphocytes, coronary sinus blood lymphocytes and peripheral blood lymphocytes after rat heart transplantation. Fisher rats served as donors and Lewis rats as recipients. Among recipients that received no immunosuppression, grafts were removed 2 days after transplantation (Ongoing Rejection Group: n = 7) and on the day of terminal rejection (Rejection Group: n = 7). The Immunosuppression Group (n = 7) was treated with cyclosporine A at a dose of 3 mg/kg/day intramuscularly for 14 days. The following two color analyses were studied: OX8 (anti-CD8) with OX39 (anti-interleukin 2 receptor; IL2R), W3/25 (anti-CD4) with OX39, W3/25 with OX8. Histological grading demonstrated no significant difference between the Ongoing Rejection Group and the Immunosuppression Group, which showed mild rejection (1.29 +/- 0.27 versus 1.14 +/- 0.24). The proportion of CD8(+)IL2R(+) graft infiltrating lymphocytes showed a more significant increase in the Ongoing Rejection Group than in the Immunosuppression Group (32.1 +/- 3.05 versus 20.6 +/- 9.02; p < 0.01). The proportion of CD8(+) IL2R(+) coronary sinus blood lymphocytes also showed significant increase in the Ongoing Rejection Group compared with the Immunosuppression Group (4.63 +/- 1.91 versus 2.52 +/- 1.60; p < 0.05). These results suggest that this technique can detect acute allograft rejection earlier than endomyocardial biopsy, before the phase in which histological findings become evident.