Dendritic cells, engineered to secrete a T-cell receptor mimic peptide, induce antigen-specific immunosuppression in vivo.
A T-cell receptor mimic peptide (TCRpep) consisting of an 8-amino-acid peptide, homologous to the transmembrane region of the T-cell receptor (TCR) alpha chain, blocks T-cell activation after systemic application. When dendritic cells (DCs) were transduced to secrete the TCRpep and injected into mice, evidence of immunosuppression was observed. In a CD8-driven allergy model, the injection of DCs transduced with the TCRpep reduced inflammation markedly and in a CD4+ T cell-dependent model of multiple sclerosis (experimental autoimmune encephalitis, EAE), injection of TCRpep-secreting DCs abrogated EAE symptoms and prolonged survival. These effects were antigen specific, because transduced DCs that did not express the respective antigen failed to convey protection in the allergy model as well as in the EAE model. Thus these data show that DCs expressing the TCRpep are able to suppress T-cell activation and might be a useful tool for inducing antigen-specific immune suppression in vivo.
Mahnke
Karsten
K
Department of Dermatology, University of Mainz, Langenbeckstrasse 1, D-55101 Mainz, Germany. mahnke@hautklinik.uni-mainz.de
Qian
Yingjie
Y
Knop
Jürgen
J
Enk
Alexander H
AH
D000818:Animals; D000941:Antigens / Q000276:immunology; D032701:Biomimetics / Q000379:methods*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D007165:Immunosuppression Therapy / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D015202:Protein Engineering / Q000379:methods*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D018000:Receptors, Peptide / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology
D000941:Antigens; D011948:Receptors, Antigen, T-Cell; D018000:Receptors, Peptide