1. ¹University Children's Hospital, Ulm, Germany
2. ²Skin Cancer Unit, German Cancer Research Center Heidelberg and University Hospital Mannheim, Mannheim, Germany
3. ³Department of Immunology, University of Ulm, Ulm, Germany

Correspondence: K-M Debatin, University Children's Hospital, Eythstr.24, 89070 Ulm, Germany. Tel.: +49 731 5002 7700; Fax: +49 731 5002 6681; E-mail: klaus-michael.debatin@uniklinik-ulm.de

Received 13 February 2006; Revised 15 May 2006; Accepted 19 June 2006; Published online 11 August 2006.

Abstract

Genetically modified antigen-presenting cells (APC) represent an attractive strategy for in vitro immunomodulation. In the human system, APC expressing HLA-A1 and a membrane-bound form of CD95L (m-CD95L) were used for selective depletion of HLA-A1-specific T cells. In short-term assays, m-CD95L-expressing APC-induced apoptosis in activated T cells and the constitutive presence of m-CD95L and HLA-A1 expressing APC in long-term T cell cultures prevented the expansion of CD4⁺ and CD8⁺ HLA-A1-specifc T cells and the development of HLA-A1-specific cytotoxicity. However, immunity towards third party, viral and bacterial antigens was maintained and T cells spared from depletion could be induced to develop cytotoxicity towards unrelated antigens. Interestingly, inhibition of HLA-A1-specific T cell response absolutely requires the coexpression of m-CD95L and HLA-A1 antigen on the same APC. Thus, m-CD95L expressing APC might be used in clinical settings to obtain tolerance induction in allogeneic transplantation systems or autoimmune diseases.