Valve interstitial cells induce donor-specific T-cell anergy

Abstract

Objectives: Valve allografts produce an immune response, which can influence their performance. The exact role of the interaction between recipient T cells and the different cellular components of the donor valve in stimulating 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 cell-surface molecules before and after interferon γ treatment by means of a panel of specific monoclonal antibodies and flow cytometry. The proliferative response of highly purified T lymphocytes was used to assess the immunogenicity 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 are either induced or upregulated after interferon γ treatment. T-cell responses to endothelial cells were detected after interferon γ treatment, but responses to interferon γ–treated interstitial cells were not detected. 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 similar range of cell-surface molecules, it is only the endothelial cells that are immunogenic. In addition, we have shown that these 2 cell types interact in a donorspecific manner to orchestrate the immune response and therefore may have clinical relevance in the allogeneic response of the heart valve recipients.

J Thorac Cardiovasc Surg 2001;122:129-35