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. T he local production of cytokines by T-helper 1 and T-helper 2 cells wi thin an allograft could influence the induction of graft rejection. Me thods: Therefore we studied the in vitro production of cytokines by ce lls infiltrating the graft. Graft-infiltrating cell cultures derived f rom human endomyocardial biopsy specimens more often produced interleu kin-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 o btained from the heart donor than after stimulation with a third-party B-cell line. Furthermore, the levels of these cytokines were signific antly higher after donor stimulation than after third-party stimulatio n p < 0.001). Results: Within the first 90 days after heart transplant ation, significantly higher levels of interleukin-2 p = 0.05) and inte rferon-gamma p = 0.02) were produced by donor-stimulated lymphocyte cu ltures derived from biopsy specimens taken during a rejection episode compared with cultures from biopsy specimens taken during a period wit hout rejection. After 90 days, the levels of T-helper 1 cytokine (inte rleukin-2 and interferon-gamma) production were, irrespective of the r ejection grade, comparable with those found in the cultures from rejec tion biopsy specimens taken early after transplantation. With regard t o T-helper 2 cytokines (interleukin-4 and interleukin-6), no relation was found with the presence of rejection at any time after transplanta tion. Conclusions: These data suggest that in the first 3 months after heart transplantation, acute rejection is associated with the product ion of increased levels of T-helper 1 cytokines but not of T-helper 2 cytokines by donor stimulated graft-infiltrating lymphocytes. Thereaft er, the T-helper 1 cytokine production of graft-infiltrating lymphocyt es remained high, suggesting a continuous state of immunologic activit y even in the absence of rejection. .