Valve interstitial cells induce donor-specific T-cell anergy

Objectives: Valve allografts produce an immune response, which can influenc e their performance. The exact role of the interaction between recipient T cells and the different cellular components of the donor valve in stimulati ng an immune response is not known. Therefore the T-cell response to valve endothelial and interstitial cells was investigated in vitro. Methods: Valve endothelial and interstitial cells were characterized for ce ll-surface molecules before and after interferon gamma treatment by means o f a panel of specific monoclonal antibodies and flow cytometry. The prolife rative response of highly purified T lymphocytes was used to assess the imm unogenicity of cultured valve endothelial and interstitial cells. This was further investigated by using a 2-step tolerance-induction protocol. Results: Valve endothelial and interstitial cells express similar levels of human leukocyte antigens and adhesion and costimulatory molecules, which a re either induced or upregulated after interferon gamma treatment. T-cell r esponses to endothelial cells were detected after interferon gamma treatmen t, but responses to interferon gamma -treated interstitial cells were not d etected. This lack of response resulted in the induction of T-cell anergy, which was reversed by the presence of the costimulatory molecule B7-1. Conclusions: Although valve endothelial and interstitial cells express a si milar range of cell-surface molecules, it is only the endothelial cells tha t are immunogenic. In addition, we have shown that these 2 cell types inter act in a donor-specific manner to orchestrate the immune response and there fore may have clinical relevance in the allogeneic response of the heart va lve recipients.