Membrane-bound CD95 ligand expressed on human antigen-presenting cells prevents alloantigen-specific T cell response without impairment of viral and third-party T cell immunity.
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-specific 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.
Strauss
G
G
University Children's Hospital, Ulm, Germany.
Osen
W
W
Knape
I
I
Jacobsen
E-M
EM
Müller
S M
SM
Debatin
K-M
KM
D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D000942:Antigens, Bacterial / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein / Q000378:metabolism*; D015788:HLA-A1 Antigen / Q000235:genetics / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007110:Immunity, Active; D007111:Immunity, Cellular; D007519:Isoantigens / Q000276:immunology* / Q000494:pharmacology; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014162:Transfection
D000942:Antigens, Bacterial; D000956:Antigens, Viral; D053222:Fas Ligand Protein; D015788:HLA-A1 Antigen; D007519:Isoantigens