DIFFERENT PATTERNS IN DONOR-SPECIFIC PRODUCTION OF T-HELPER-1 AND T-HELPER-2 CYTOKINES BY CELLS INFILTRATING THE REJECTING CARDIAC ALLOGRAFT

Background: Cytokines play an important role in allograft rejection. The local production of cytokines by T-helper 1 and T-helper 2 cells within an allograft could influence the induction of graft rejection. Methods: Therefore we studied the in vitro production of cytokines by cells infiltrating the graft. Graft-infiltrating cell cultures derived from human endomyocardial biopsy specimens more often produced interleukin-2 p < 0.001), interferon-gamma p < 0.001), interleukin-4 (p = 0.02), and interleukin-6 (p = 0.04) after stimulation with a B-cell line obtained from the heart donor than after stimulation with a third-party B-cell line. Furthermore, the levels of these cytokines were significantly higher after donor stimulation than after third-party stimulation p < 0.001). Results: Within the first 90 days after heart transplantation, significantly higher levels of interleukin-2 p = 0.05) and interferon-gamma p = 0.02) were produced by donor-stimulated lymphocyte cultures derived from biopsy specimens taken during a rejection episode compared with cultures from biopsy specimens taken during a period without rejection. After 90 days, the levels of T-helper 1 cytokine (interleukin-2 and interferon-gamma) production were, irrespective of the rejection grade, comparable with those found in the cultures from rejection biopsy specimens taken early after transplantation. With regard to T-helper 2 cytokines (interleukin-4 and interleukin-6), no relation was found with the presence of rejection at any time after transplantation. Conclusions: These data suggest that in the first 3 months after heart transplantation, acute rejection is associated with the production of increased levels of T-helper 1 cytokines but not of T-helper 2 cytokines by donor stimulated graft-infiltrating lymphocytes. Thereafter, the T-helper 1 cytokine production of graft-infiltrating lymphocytes remained high, suggesting a continuous state of immunologic activity even in the absence of rejection. .