Valve interstitial cells induce donor-specific T-cell anergy.
OBJECTIVE
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 gamma 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 gamma treatment. T-cell responses to endothelial cells were detected after interferon gamma treatment, but responses to interferon gamma-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 donor-specific manner to orchestrate the immune response and therefore may have clinical relevance in the allogeneic response of the heart valve recipients.
Batten
P
P
Division of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College of Technology, Science and Medicine at Harefield Hospital, Harefield, Middlesex, United Kingdom. puspa.batten@harefield.nthames.nhs.uk
McCormack
A M
AM
Rose
M L
ML
Yacoub
M H
MH
D000911:Antibodies, Monoclonal; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology*; D004727:Endothelium / Q000276:immunology*; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology; D006351:Heart Valves / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D007371:Interferon-gamma