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J Thorac Cardiovasc Surg 2001;122:129-135
© 2001 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology (CSP)

Valve interstitial cells induce donor-specific T-cell anergy

Puspa Batten, PhD, Ann M. McCormack, BSc, Marlene L. Rose, PhD, Magdi H. Yacoub, FRS

From the Division of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College of Technology, Science and Medicine at Harefield Hospital, Harefield, Middlesex, United Kingdom.

Received for publication Sept 19, 2000. Revisions requested Jan 18, 2001; revisions received Jan 26, 2001. Accepted for publication Feb 5, 2001. Address for reprints: Puspa Batten, PhD, Division of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College of Technology, Science and Medicine at Harefield Hospital, Heart Science Centre, Harefield, Middlesex UB9 6JH, United Kingdom (E-mail: puspa.batten@ harefield.nthames.nhs.uk

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 {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 donorspecific manner to orchestrate the immune response and therefore may have clinical relevance in the allogeneic response of the heart valve recipients.


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