Increased numbers of circulating donor-specific T helper lymphocytes afterhuman heart valve transplantation

Implantation of cryopreserved human donor heart valves for either congenita l or acquired cardiac disease has been performed since the last three decad es. Although the clinical outcome is good, long-term valve degeneration res ulting in dysfunction has been observed. A specific immunological response of the recipient against the allograft has been proposed as one of the fact ors involved in this process. Helper T lymphocytes play an important interm ediate role in cellular and humoral immune response. Increasing numbers of circulating donor-specific helper T lymphocytes precursors (HTLp) correlate with graft rejection after organ transplantation. To investigate whether c ryopreserved human donor heart valves are able to induce a donor-specific T helper response, we monitored the HTLp frequencies (HTLpf) in peripheral b lood samples of 13 patients after valve allograft transplantation by use of a limiting dilution assay followed by an interleukin-2 bioassay. Prior to transplantation, HTLpf specific for donor and third-party antigens showed i ndividual baseline levels. After allografting, the antidonor frequencies si gnificantly increased in 11 of the 13 patients (P = 0.02). This was not fou nd for stimulation with third-party spleen cells (P = 0.68), which indicate s a donor-specific response. Maximal donor-specific HTLpf were already foun d at 1-2 months after operation. Valve allograft transplantation induces an increase in the numbers of donor-specific HTLp in peripheral blood of the patients. Analogous to organ transplantation, these HTLp may play a crucial role in events that lead to valve damage. Therefore, monitoring of HTLp in peripheral blood samples might be informative for donor valve degeneration (rejection) and subsequently valve allograft failure.